HK1165978B - Compact storage of auxiliary analytical devices in a cartridge - Google Patents

Description

Space-saving storage of analytical aids

Technical Field

The invention relates to an analysis magazine (Magazin) for accommodating a plurality of analysis aids (Hilfsmitte) and to an analysis system which is designed to interact with an analysis magazine according to the invention. Analytical magazine and analytical system of this type are used in natural science, technology, medicine and/or medical (medizinisch) diagnostics for the qualitative (qualitaiv) or quantitative (quantitaiv) detection (nachweisen) of one or more analytes in a sample. For example, the sample may be a sample of a bodily fluid, such as urine, blood, interstitial fluid, or the like. The analyte to be detected may for example be a metabolite. Without limiting the other possible fields of application, the invention is described below with reference to the blood glucose (blutgukose) test. In principle, however, other analytes can alternatively or additionally also be measured, wherein the analyte concept can also comprise other measurable properties of the sample, for example coagulation (koagulane) or the like.

Background

Systems are known in particular from the field of clinical diagnostics, but also from other fields, by means of which analytes in a sample can be detected. In clinical diagnostics, tests of this type (e.g., blood glucose tests) generally involve the production of a sample of a body fluid (e.g., blood or interstitial fluid) which is then contained and subjected to qualitative and/or quantitative analysis. For this purpose, one or more analytical aids (Hilfsmittel) are generally used, which can comprise, for example, lancets (Lanzette) and/or test elements, by means of which samples can be generated and/or received and/or analyzed.

In particular, in this type of divisionIntegration of different system functions in analytical systems (e.g. blood glucose measuring systems) has led in the past to commercial solutions with exchangeable cartridges (e.g. assay strip cartridges) for analysis aids. A typical representation of this product family is Accu-Chek CompactAnd the Ascensia Breeze system, which represents a commercially available system. A typical accessory cartridge typically includes 17 or 10 test strips.

In the case of new systems, in many cases different system functions, such as, for example, the system function for the production of a sample (for example, by perforation of a skin portion) and the system function for receiving a sample and optionally the system function for likewise analyzing, are combined in an integrated manner. In the case of a more integrated system, for example, blood acquisition and assay functions may be performed together. For this purpose, so-called microsampiers (microsampiers) are known, which combine the lancet function with the sample-conveying function (for example, the conveyance of a sample to an assay element). This saves separate puncture aids for taking blood, for example from a finger pad (fingerbee), an earlobe or other skin part of a test subject (Proband).

In this case, a plurality of microsamplers of this type can be accommodated in replacement cartridges of different design. In principle, irrespective of the type of analysis aid, three main types of Magazine can be distinguished, namely circular magazines (for example in the form of rollers and/or disks), linear magazines (for example in the form of stacking magazines (Stapelmagazine), zigzag magazines (zigzag-Zack-Magazine) or the like), and tape magazines, in which the analysis aid is arranged on a tape or on another form of at least partially flexible carrier. In principle, these types of cartridges can also be used or modified within the scope of the invention described below. Circular cartridges are described in the prior art, for example in documents US 2006/0008389, US 2007/0292314, US2006/0184064, US 2003/0212347 or US 2002/0087056. Linear cartridges are described, for example, in documents US 6,036,924 or US 2003/0191415. Strap magazines are disclosed, for example, in documents US 2002/0188224, US 2008/0103415, EP 1360935a1 or DE 19819407a 1.

The impetus for the integration of multiple system functions is especially the desire for simple and reliable operation and for miniaturization of the overall system. Since it is relatively inconvenient to change the magazine frequently and carries the risk that at the critical moment there is no spare magazine at hand, the magazine should contain at least 25 test elements, preferably even 50 or more test elements.

However, the systems and cartridges known from the prior art technically comprise some challenges. Thus, for example, the requirement for a system size which is as small as possible, while the largest possible number of analytical aids (e.g. test elements) per magazine, represents a conflict of objectives (Zielkonflikt). Device volumes below 130ml are particularly preferred for the operator (Anwender). However, this is not commercially available, and the structural dimensions are combined with a cartridge comprising, for example, 50 microsamplers.

Furthermore, circular magazines such as the one described above have the disadvantage that the number of analysis aids usually has a direct influence on the outer diameter of the circular magazine. This results in a high storage capacity or very flat storage pocketsDevices (e.g. in disk magazines) or devices resulting in a particularly thick device (e.g. in drum magazines). However, this type of device does not meet customer expectations in many cases. On the other hand, in linear magazines, the number of analytical aids available is usually reflected directly (eingehen) over the length of the magazine. Furthermore, in this solution, the magazine is usually pushed after each assay, so that the space requirement for the magazine must be doubled in the system (vorhalten). Most likely (Am ehesten) to achieve the desired system scale via a tape magazineIn size, since the cartridge size is non-linearly related to the cartridge capacity. However, in systems of this type, a high mechanical complexity is disadvantageous in many cases, in particular with regard to the belt guidance and/or the belt control.

It is therefore known from the prior art to provide the magazine in the form of a so-called flip magazine (Wendemagazine). Thus, for example, a linear magazine for lancets is described in document US2006/0264996, which is designed in a double (verdoppeln) manner by two magazines of this type being joined together end-to-end. After all the lancets of the first end section of the entire magazine thus produced have been used up, the magazine is ejected (auswerfen), turned over and the lancets in the second end section are used.

However, a disadvantage of this type of tipping magazine known from the prior art is that it is designed only for use in a piercing aid. The known tilting cartridges are not suitable for the (gerecht) integrated idea of being used in systems in which a plurality of system functions are integrated. However, an integrated system of this type, in particular a system with so-called microsampler magazines, has a series of special requirements. Therefore, it is often necessary to detect the analyte in the cartridge, for example optically and/or electrochemically. Furthermore, the integrated test element (e.g. test chemistry) should be durable in its durabilityThe aspect has a guarantee so that a reliable validity period of use (Aufbrauchfrist) can be indicated (angelen). Furthermore, cross-contamination of the analysis aids, in particular of the microsampler, should be avoided. In the known analysis systems and the known analysis cartridges, these requirements have hitherto not been met or have only been met insufficiently.

Disclosure of Invention

It is therefore an object of the present invention to provide an analysis cartridge and an analysis system which at least avoid the disadvantages of the known cartridges or systems as much as possible. In particular, the analysis cartridge should be designed for use in a microsampler system.

This object is achieved by an analysis cartridge and an analysis system with the features of the independent claims. Advantageous developments of the invention which can be implemented individually or in combination are indicated in the dependent claims.

An analysis cartridge is proposed, which comprises a plurality of analysis aids, preferably at least 10 analysis aids, in particular at least 20, at least 30, at least 40 and particularly preferably at least 50 or more analysis aids, which are accommodated in a chamber. The assay cartridge is for use in an assay system. An analysis system is understood here in general as a system which fulfills at least one analysis function. An analytical function is understood here to mean the detection of at least one analyte in a sample. Here, the starting point is, without limitation, that the sample is a sample of a body fluid. However, other samples can in principle also be analyzed. Likewise, the concept of at least one analyte is to be understood in principle broadly and includes, for example, one or more metabolites in addition to the substance to be detected, and in principle also other measurable properties of the sample. Particularly preferably, however, the present invention applies to the detection of at least one metabolite in a body fluid, for example for the detection of blood glucose, cholesterol, (anti-) coagulants (Koagulantien) or the like.

Accordingly, an analysis cartridge is understood to be a cartridge which is designed for use in an analysis system of this type. For example, for this purpose, the magazine may comprise one or more housings which can be inserted into one or more housings of the analysis system. For this purpose, for example, corresponding orientation aids, connecting elements, rails, hooks, grooves, projections, transport elements or combinations of the mentioned and/or other elements, which make possible or at least simplify the interaction of the analysis cartridge with the analysis system, can be provided at the analysis cartridge. For example, transport elements and/or positioning aids can be provided, which enable positioning or exact orientation of the magazine within the analysis system.

Accordingly, an analytical aid is understood to be an aid which is designed to make it possible for the analytical system to detect at least one analyte in a body fluid and/or to interact at least partially with a component of the analytical system when detecting at least one analyte in a body fluid. In particular, the analytical aids can be single-use (Einweg) aids (disposables), i.e. aids which are intended for a single use. The analysis cartridge comprises a plurality of chambers, i.e. at least two chambers, in which at least one of the analysis aids is or can be accommodated, respectively. For example, exactly one analytical aid can be accommodated in each chamber. E.g. in the form of discs or rodsThis may be the case in an analysis cartridge. Alternatively, a plurality of analytical aids is also accommodated or can be accommodated in one chamber. This can be achieved, for example, in a tape magazine, in which, for example, a good reel (Gutwickel) with a plurality of unused analytical aids is accommodated in the first chamber and a defective reel (Schlechtwickel) on which a plurality of used analytical aids can be accommodated in the second chamber. The analytical aids can likewise again be composed of partial aids, which can be designed to be coupled togetherOr they can likewise be designed independently of one another, for example can be handled or applied independently of one another. The totality of all the partial aids in the chamber (often referred to in colloquial as "assay" is then generally understood to be an analytical aid in the context of the above definition.

In particular, the analysis aids may comprise one or more of the types of analysis aids (also referred to as partial aids) described below. The analysis aid may thus, for example, comprise at least one test element, for example respectively at least one test element, wherein the at least one test element has at least one test chemical which is designed to change at least one property in the presence of the analyte to be detected. The assay chemistry may, for example, be designed in the form of one or more assay regions. In this case, the assay chemical can be incorporated, for example, at least partially in the housing of the analytical cartridge, in particular in the wall of the chamber. For example, the assay chemicals can be designed such that at least one assay region is allocated to the inner space of one chamber. In this case, the assay chemistry can also be designed for several or all chambers simultaneously, for example in the form of a common assay area for several or all chambers of the analysis cartridge. For example, an assay chemistry disk may be provided, for example in the form of an assay chemistry ring, wherein at least a portion of the surface of the assay chemistry disk (e.g., the assay chemistry ring) respectively faces the inner space of the chamber, such that these regions respectively form self-contained assay regions in a single chamber.

The at least one property from which the presence and/or absence of the at least one analyte can be qualitatively and/or quantitatively inferred may, for example, comprise at least one property which can be measured chemically and/or physically. Here, it can be, for example, an electrochemically and/or optically measurable property, such as a color change or the like. In particular, in the diabetes art&Volume 10 of therapeutics, supplement 1, 2008, pages 10 to 26 by J.Et al (J.et al.，Diabetes Technology&Therapeutics, Volume 10, Supplement 1, 2008, Seiten S-10 bis S-26) describe examples of this type of assay chemistry that in principle can also be applied within the scope of the invention. This is achieved byIn addition, reference may be made, for example, to document WO2007/012494 a1, in which among others moisture-resistant (feuchighteitsstabile) assay chemicals are described. The assay chemicals mentioned in these documents may also be applied within the scope of the present invention individually or in combination. In particular, quite specific assay chemistries may be applied, in which the detection specifically reacts to at least one analyte. In principle, other types of assay chemicals may be applied as well.

Alternatively or additionally to the test element, the analytical aid can also comprise one or more lancets for producing at least one hole in the skin of the test subject. A lancet is understood here in general to mean a device which produces a hole of the type through which a body fluid can be extracted from the tissue of a test subject, for example by pricking and/or cutting. For example, the lancet may comprise at least one tip and/or at least one cutting portion (Schneide) for this purpose. In particular, the lancet can be a round lancet and/or a flat lancet (Flachlanzette), i.e. a lancet which is produced, for example etched, from a flat structural element (for example a metal sheet)The lancet is provided.

Alternatively or additionally to the auxiliary means mentioned, the at least one analysis auxiliary means may comprise at least one transport element for receiving the body fluid sample and/or for transporting the sample, in particular for transporting the sample to at least one assay chemical, for example an assay chemical of the type described above. A transport element is understood here to mean, for example, an element which receives a sample and then transports it while performing a movement toward the test element. However, alternatively or additionally, other transport mechanisms may also be applied, for example transport mechanisms that are based on capillary forces. Thus, again, the analysis aid can also alternatively or additionally comprise one or more capillary elements for receiving and/or transporting a sample of the body fluid, in particular to at least one test element. Capillary elements are generally understood here to mean elements which perform a transport action and/or a collection action by means of capillary forces.

The possibilities mentioned can also be combined individually or in groups. Thus, the analysis aid may also comprise, for example, one or more microsamplers. This type of microsampler may include a spatially compact combination of a aspirating (saugend) needle and an assay element (Verzahnung). Thus, the blood to be analyzed can be transported from the wound or the hole to the test element, for example, without the aid of an operator. For this purpose, for example, a lancet with a capillary channel for suction (e.g., a needle) can be used again. In general, the microsampler should comprise at least one lancet for producing at least one hole in the skin of the test subject and at least one capillary element for receiving and/or transporting a sample of the body fluid, wherein the transport can preferably take place again at least partially towards the at least one test element. However, the transport can additionally be supported by spatial movements of the microsampler, for example by means of at least one actuator (Aktor).

The invention is described below with reference to a preferred possibility in which the analysis aid is at least partially designed to receive a sample of a body fluid during a sample extraction movement and to completely or partially transport the sample to the test element. In this context, a sample extraction movement is understood to mean, in general, a movement of the analysis aid and/or of the partial aid, which is carried out from the analysis system first toward the skin surface of the test object and then in the opposite direction toward the system. In this case, in the forward movement (Hinbewegung), for example Perforation (Perforation) of the skin can be performed, for example by means of one or more of the lancets mentioned. Sample extraction (e.g., sample collection) may be performed already during and/or after the perforation, for example, by simply applying the sample to the transport element and/or drawing the sample into the transport element (e.g., capillary element). Subsequently, a reverse movement of the analysis aid can be carried out, which can likewise be a component of the sample extraction movement. In the sample extraction movement, in particular in the reverse movement or after the reverse movement, the sample can be transported to the test element, which can be a component of an analysis aid, which can participate in the sample extraction movement and/or can also be accommodated in the chamber as an at least partially immobile partial aid. Examples will be described in detail below. For example, the sample can be transferred to the at least one test element during, or after, a later-described restocking of the analysis aid, i.e. a process in which the analysis aid is completely or partially restocked in a chamber, in particular a chamber from which the analysis aid was previously removed.

In principle, at least two principles of accommodation in the chamber are conceivable when accommodating the analysis aid in the chamber. Thus, for example, each chamber can accommodate an analytical aid, in particular an analytical aid which comprises at least one partial aid in the form of an assay element with an assay chemical. Optionally, preferably additionally, each chamber may be provided with at least one further partial auxiliary means in the form of a lancet and/or a microsampler. In this principle, the analytical aids can be stored in the same chamber, in particular after use. Alternatively, however, a further storage in another chamber is also possible. In particular in disk-shaped or rod-shaped storage containers, this first principle is preferred. According to another principle, at least one first chamber is provided for unused analytical aids and at least one second chamber is provided for used analytical aids. In this case, for example, for use, the analysis aid may be removed from the first chamber and transferred after use into a second chamber, which may be configured to be spatially separated from the first chamber. This principle can be used, for example, for tape magazines, wherein, for example, a good reel for receiving unused analytical aids can be provided in the first chamber and a defective reel for receiving used analytical aids can be provided in the second chamber.

According to the invention, it is proposed, in particular in a first aspect of the invention, that the analysis cartridge is designed such that it can be accommodated in the analysis system in at least two orientations. In particular, the analysis cartridge can be designed such that it can be coupled to the same interface of the analysis system in at least two orientations, for example with at least one transport function and/or at least one actuator function (for example for carrying out a sample extraction movement) and/or at least one measurement function (for example an optical and/or electrochemical measurement function).

For this purpose, the analysis cartridge is designed, for example, at least partially with symmetry, in particular about at least one axis of symmetry. Accordingly, the analysis cartridge can be designed, for example, as a flip cartridge, which can be inserted into the analysis system in at least two orientations and can preferably be coupled there to the same interface in all orientations.

In this context, orientation is generally preferably understood to mean the angular orientation of the analysis cartridge, for example relative to a coordinate system of the analysis system, i.e. the orientation in terms of one or more angular coordinates, for example spatial angular coordinates. Alternatively or additionally, however, an orientation may also be understood as an absolute orientation, for example if one or more cartesian coordinates are used. Particularly preferably, however, the magazine is designed, for example, as a flip magazine in such a way that the analysis magazine can be removed from the analysis system in a first orientation, after which the analysis magazine can be rotated by one or more angles for the purpose of subsequently accommodating the analysis magazine in the analysis system again in at least one second orientation, which is different from the first orientation. In particular, the rotation may be a rotation about the axis by 180 °, optionally followed by at least one further rotation, for example a rotation misaligned by an angle about an axis rotated by 90 ° with respect to the first axis, for example by a misalignment angle described in detail below. For example, the magazine can be designed entirely as a flip-over magazine, so that the two orientations are distinguished from one another by 180 ° with respect to the axis of rotation.

In particular, the analysis cartridge can be designed such that it does not allow other orientations than the desired at least two orientations that differ from one another. For example, as shown above, one or more elements can be provided which make it possible for the analysis cartridge to be inserted into the analysis system just in the set orientation and not in other orientations. For example, the housing of the analysis cartridge can be designed such that it makes it possible to insert the analysis cartridge into the analysis system only in the set orientation and not conversely in other orientations. For this purpose, the housing may for example have a corresponding shape, for example a symmetrical shape in the above-defined idea, for example a symmetry with respect to one or more rotation axes. The housing can also have corresponding elements, such as grooves, rails, projections, grooves or the like, which prevent the analysis cartridge from being inserted into the analysis system in an unset orientation.

The analysis magazine is thus configured to supply a plurality of analysis aids to the analysis system in different orientations, for example by means of a plurality of chambers with at least one analysis aid in each orientation. These analytical aids can be provided, for example, one after the other, for example, by corresponding transport mechanisms of the analytical system, which bring each chamber available in the orientation one after the other into the application position (applicationposition). In this way, the analysis magazine differs, for example, from a simple drum magazine, although the drum magazine is likewise arranged in a different orientation after the drum has been moved on (weiterkaten) to the next chamber in a clocked manner, in which orientation, however, only one analysis aid is provided.

An orientation is therefore understood as meaning in its entirety an orientation of the analysis magazine in which an analysis aid can be supplied to the analysis system from the partial magazine belonging to the orientation. Preferably, an orientation is associated with exactly one partial cartridge in each case. In this case, each orientation can be divided into a plurality of partial orientations, for example the angular positions of the magazine disk, which can be successively occupied (einnehmen) as the cycle continues. However, this sub-orientation is associated as before with the orientation of the analysis cartridge, for example with an orientation in which part of the cartridge is located in the application plane (applikationebene) and/or the application position of the analysis system. Until the orientation is changed, for example by turning the analysis cartridge over by 180 °, another part of the cartridge does not reach the application plane or application position and its analysis aids can be provided to the analysis system.

At least one sample extraction movement according to the above definition can be performed by means of an analysis aid. In particular, the analysis system can comprise one or more application positions, wherein the analysis system can be set up to use at least one chamber located exactly in the application position, in particular at least one auxiliary tool in this chamber, for the sample extraction movement. For example, the analysis system may comprise one or more actuators by means of which a sample extraction movement may be performed. In the sample extraction movement, the entire analysis aid can be moved and/or, if appropriate, only at least one part of the aid can be moved. If the analysis aid comprises, for example, at least one lancet and/or at least one microsampler and/or at least one transport element, the lancet or microsampler or transport element can be used for the sample extraction movement, while on the other hand other parts of the analysis aid (for example one or more test elements) can remain in the chamber. However, other designs are also possible, for example designs in which the test element completely or partially participates in the sample extraction movement. However, embodiments are described below in which the test element is left within the chamber, and the microsampler, on the other hand, performs a sample extraction movement and transports the body fluid sample into the chamber towards the test element.

In this case, in a first aspect of the invention, the analysis cartridge is designed such that a restocking of the analysis aid is possible. In this context, restocking is understood to mean a process in which the analysis aid is transferred back again completely or partially into the same chamber (from which the analysis aid is likewise removed), or alternatively or additionally into a separate chamber, preferably during or after the complete execution of the sample extraction movement. In accordance with the invention, the analysis cartridge is therefore generally designed such that a return of this type is technically possible and is not impeded by barbs or similar design, for example.

For the purpose of restocking, for example, the analytical aids can also be designed to interact with the analytical system in such a way that this type of restocking is possible. The analysis aid can thus have, for example, at least one coupling element, by means of which a restocking of the analysis aid is possible, in particular into a chamber from which the respective analysis aid is removed. For example, the coupling element may have one or more grooves, hooks, protrusions, recesses, eyeletsGuide holeOr other coupling elements or combinations of the mentioned and/or other coupling elements. Coupling elements of this type are available, for example, from the prior art. For example, reference may be made to a coupling element described in document US 2006/0008389a1, in which the actuator is coupled to the analysis aid by means of one or more hooks and then decoupled again from the analysis aid, for example for sample extraction movements and subsequent restocking. Coupling elements of this type may also be used within the scope of the invention. In principle, however, other types of coupling can also be used, for example a friction-fit or form-fit coupling of the actuator to the analytical aid and/or to a part of the analytical aid, for example by means of a gripper or the like.

In particular, one or more actuators can be coupled to the coupling element, which actuators are, for example, coupling rods, which can be a component of the analysis system and which cause not only the pushing of the analysis aid, but also the return stroke (ricktrieb) and the subsequent restocking of the analysis aid in the region of the sample extraction movement. For example, corresponding coupling rods, tappets or the like can be provided.

In a first aspect of the invention, the analysis magazine is configured to support (holtern) the analysis aid or a part of the aid in the chamber after restocking. Support is understood to mean a process in which the analysis aid is at least largely prevented from falling out of or slipping out of the chamber, for example through a hole created in a cover (Versiegelung) of the chamber during the sample extraction movement. For this purpose, one or more holding elements, for example at least one holding element per chamber, can be provided in the analysis magazine and/or in the analysis aid or in part of the aid, which holding elements bring about this type of support after restocking. For example, the holding element may comprise a hook, a constriction (Engstelle), a projection, an eyelet, a detent (Sperre) or the like or a combination of the mentioned and/or other elements. In this case, a partial holding element can also be provided on the analysis aid or on the partial aid, respectively, which interacts with a corresponding partial holding element of the chamber.

Alternatively or additionally to the use of one or more holding elements, the support of the analytical aids can also be realized in other ways after restocking. For example, the analysis aid can also be supported at least partially in a form-fitting and/or force-fitting manner. For example, the form fit and/or force fit can also be achieved during and/or after restocking. Thus, for example, the analytical aid and/or a part of the analytical aid can be introduced into a restocking position in the magazine, for example in the chamber, during restocking, in which the force fit and/or the form fit only occurs. The restocking position may be the same as or different from a position in which the analysis aid and/or part of the aid is in the position prior to the sample extraction movement. For example, a form fit and/or force fit can also be combined with a deformation of the analysis aid and/or of the partial aid. For example, the chamber can be designed such that the analytical aids and/or parts of the aids (e.g. lancets and/or microsamplers) are bent in the chamber and are preferably pressed against the chamber wall by a restoring force (rueckstellkuft). In this way, a force fit, in particular a friction fit, can be achieved. For example, the chamber may be designed to be curved, so that the analysis aid and/or parts of the aid are curved in the chamber. The lancet or the microsampler may, for example, be completely or partially made of an elastic material, for example a metallic material, for example a metal sheet, which may provide the above-mentioned restoring force. Alternatively or additionally, the chamber may also be provided, for example, with a resilient wall which can be deformed by the analytical aid and/or by parts of the analytical aid during restocking, wherein the restoring force of the chamber wall can cause the mentioned force fit, in particular a friction fit. In this way, the corresponding support of the restocked analytical aid can thus be brought about by a matching of the chamber geometry and/or the geometry of the analytical aid and/or a suitable selection of the material of the analytical aid and/or of the housing. Combinations of the mentioned possibilities and/or other possibilities are likewise conceivable for the support.

In a first aspect of the invention, the analysis cartridge comprises at least two substantially identical partial cartridges, wherein each partial cartridge may comprise a plurality of analysis aids, for example of the same type, which may, for example, each be accommodated in a single chamber. In this case, substantially identical partial cartridges are understood to mean cartridges which are designed identically such that they can be replaced by one another in the above-mentioned possible different orientations of the analysis cartridge. For example, each partial magazine can be provided with a certain orientation of the analysis magazine, which may also be referred to as the application orientation, and in which the respective partial magazine can interact identically with the analysis. For example, the analysis system can have an application position, wherein, in the application orientation, one of the partial cartridges is arranged in the application position and/or in the application plane of the analysis system and/or an analysis aid or a partial aid can be provided at the analysis system. Preferably, however, the partial cartridges do not have to have the same number of analytical aids in each case.

For example, two partial pockets stacked one above the other can be provided. For example, a partial cartridge may make it possible to reinsert the cartridge into the analysis system after a rotation of 180 ° and optionally at least another rotation about another axis (e.g. an angular misalignment rotation). The partial pockets can, for example, be arranged in different planes, for example in the form of partial pockets stacked one above the other. The stacking is carried out in such a way that, after a change from one possible orientation (Wechsel) to another possible orientation, the partial magazines respectively belonging to this orientation can interact with the analysis system, for example with the same interface of the analysis system, which preferably is adapted to all orientations. In this way, the analysis cartridge differs, for example, from a cartridge in which simple test elements are arranged next to one another.

Advantageously, the analysis cartridge can be further designed in different ways. As already described above, the analysis cartridge can therefore be designed at least partially with symmetry, in particular about at least one axis of symmetry.

The analysis cartridge can in particular have at least one display element, preferably a plurality of display elements, the number of which can correspond, for example, to the number of possible orientations. The display element can be designed to be detected by the evaluation system (erfassen) and to provide at least one piece of information about the current orientation to the evaluation system. The display element may comprise, for example, at least one simple, unchangeable element, which is detectable by the analysis system. However, the display element may alternatively or additionally also comprise one or more variable elements (which may be changed, for example, by the analysis system), such as a membrane element (which may be pierced through after use of the chamber), a magnetic memory element which may be written by the analysis system (beschreiben), or the like.

In the analysis magazine, the analysis aids can be arranged in at least two aid planes, wherein after the orientation change in the analysis system, the new aid planes are each arranged at least partially in the application plane of the analysis system. An application plane is understood to be a plane of the analysis system which has at least one application position, i.e. a position in which an analysis aid can be used by the analysis system, for example for lancet movement, sample extraction movement, measurement of the analyte concentration or the like. The auxiliary tool plane is understood to be a common plane of the analytical auxiliary tool accumulations (Ansammlung) that can be used in the same orientation, which can, for example, be arranged in the same plane in practice or can also be slightly offset relative to this plane.

In principle, the analysis magazine can have one or more of the basic shapes already described above and/or other shapes, for example the shape of a circular magazine (for example in the form of a drum and/or a disk), a linear magazine (for example a stacked magazine and/or a zigzag magazine) and/or a strip magazine. In this connection, reference may be made, for example, to the prior art, wherein, according to the invention, the systems described in the prior art can be modified to a flip-over magazine or an analysis magazine which can be accommodated in an analysis system at least in two orientations. It is particularly preferred that the analysis magazine is designed in the form of a circular magazine, in particular in the form of a circular disk, wherein the analysis aids are preferably oriented in the analysis magazine at least approximately in a radially arranged manner. In this type of disk magazine (which can comprise analysis aids, for example, in at least two aid planes), the advantage of turning the magazine over is particularly pronounced, since the magazine capacity can be increased without having to enlarge the diameter of the circular disk. Since the thickness of the disc is usually significantly smaller than its diameter, the increase in thickness, for example by providing a plurality of auxiliary tool flats, is not significant in design terms as compared to the enlargement of the radius of the disc. However, in principle, analytical cartridges (for example stick-shaped cartridges and/or strip-shaped cartridges) which differ from disk-shaped cartridges can also be provided according to the invention.

If the analysis magazine is designed completely or partially as a circular magazine, in particular in the form of a circular disk, it is particularly preferred if the analysis aids in the different aid planes are arranged angularly offset from one another. For example, in a first auxiliary tool plane, the analysis auxiliary tools can be oriented radially at equal distances, which is also the case in a second auxiliary tool plane different from the first auxiliary tool plane. In this case, it is particularly preferred to establish the mentioned angular offset, so that, for example, in a projection between two adjacent auxiliary tools of the first auxiliary tool plane onto the second auxiliary tool plane, an analysis auxiliary tool is arranged between two analysis auxiliary tools of the first auxiliary tool plane with exactly the angular offset. In this way, it is possible to ensure that all auxiliary tools of all auxiliary tool planes can be accessed from two directions perpendicular to the auxiliary tool planes which are preferably arranged parallel to one another, without this access being impeded by analytical auxiliary tools in the other auxiliary tool planes, for example.

It is therefore often particularly preferred that the different auxiliary tool planes are arranged parallel to one another. In general, it is also preferred in embodiments other than those described to configure the analysis magazine in such a way that access to the chamber in the application position of the analysis system and/or to the at least one analysis aid accommodated therein is possible from at least two directions, in particular from directions opposite one another, in particular from a direction perpendicular to the plane of the aid, in all possible orientations of the analysis magazine in the analysis system.

In particular, however, an analytical magazine according to the invention with a high packing density (Packungsdicht) can also be produced in other ways by means of one or more of the embodiments described above. In particular, high packing densities (Packungsdichte) of this type can be produced in particular in the case of the circular cassettes mentioned, in particular in the case of the disk-shaped cassettes mentioned, in a radial orientation. In comparison with the prior art, in which such an increase in the packing density is generally associated with an increase in the radius, at a radius which remains the sameA high packing density is achieved. In particular, such an analysis cartridge can be produced in such a way that it has one or more of the following properties: not more than 10cm³Preferably not more than 8cm³And particularly preferably not more than 7.5cm³Total volume of (d); an outer radius of not more than 5cm, preferably not more than 3cm, and particularly preferably not more than 2.5 cm; an inner radius of between 0.5cm and 2cm, in particular between 1.0cm and 1.5cm, and particularly preferably about 1.2 cm; a thickness of not more than 1cm, particularly preferably not more than 0.5 cm; between 10 and 100, in particular between 20 and 70, and particularly preferably 50 analytical aids; at 3cm³To 30cm³In particular in the range of 5cm³To 10cm³And especially preferably 7.5cm³The volume of (a); greater than 5/cm³In particular at 5/cm³And 10/cm³In between (e.g. at 6/cm)³To 7/cm³In between) and particularly preferably 6.7/cm³The packing density of the analysis aid of (1). For example, the analysis cartridge can be designed as a disk-shaped cartridge with an outer radius of about 2.5cm, an inner radius of about 1.2cm, a thickness of about 0.5cm, a number of 50 analysis aids and thus 7.5cm³Volume of (2) and 6.7/cm³The packing density of (2).

The packing density is understood here to be the ratio of the number of analysis aids and/or the number of chambers to the structural volume of the analysis cartridge. For example, with a simple disc with a diameter of 50mm and a thickness of about 3mm (which may for example have, for example, 50 analysis aids/5.42 cm³Packing density of) in comparison, the packing density can be 50 analysis aids/5.97 cm in an inversion disk according to the invention with a diameter of 50mm³(that is, for example, 50 chambers). Regardless of their function and design, the analytical aids are often also referred to as "assay parts" here. In this case, the test section is therefore generally understood to mean at least one analytical aid which can be used for the test procedure. The test element or the lancet or both can be the test element and the lancetThe pairs of components, which can be combined and can be used for a common sample extraction and subsequent analysis, wherein preferably exactly one assay part is stored (lagern) in exactly one chamber. Thus, the analysis aid or assay part may also comprise, for example, a plurality of partial aids combined together. It is particularly preferred that each analysis aid comprises at least one analysis portion aid in the form of an assay element with an assay chemical. Alternatively or preferably additionally, each analysis aid may furthermore comprise an analysis part aid in the form of a lancet and/or a microsampler. For example, exactly one chamber can accommodate an analytical aid or test element in each case. However, within the scope of the invention, no distinction is made here and below in language and context between the test part and the analysis aid, including the possibility that the test part or the analysis aid may comprise a plurality of partial aids, for example a test element and a lancet, respectively. The flipping disk may for example have a thickness of 5mm and a diameter of 42 mm. In the case mentioned, the central opening in the magazine is considered in each case, since this installation space can also be used for the device mechanism

As indicated above, the analysis aid can be designed, in particular, at least in part as a so-called microsampler, i.e. as an analysis aid which is intended to make it possible to generate and receive a sample and optionally also to analyze the sample. For this purpose, the microsampler may for example comprise at least one lancet and at least one capillary element. In general, the analysis aid can be designed at least in part to receive a sample of the body fluid during the sample extraction movement and to transport the sample to the test element, wherein the transport of the sample can take place, in particular, at least in part during the restocking of the analysis aid.

As indicated above, the analytical aid can have an assay chemical, in particular, which can be set to change at least one property in the presence of the analyte to be detected. For example, reference may be made to known assay chemicals of the type described above, which may also be applied within the scope of the present invention. In particular, the assay chemical may be comprised in the form of at least one assay region. In particular, an assay region of this type may be at least partially accommodated in the chamber. For example, the assay region may be completely or partially introduced into the chamber and/or may also be incorporated into the chamber, for example into a chamber wall. For example, the assay region may be housed in a chamber wall and/or on and/or in an aperture housed in the chamber wall, the surface of the assay region being allocated to or accessible from the interior of the chamber, respectively. The analysis system may support the transfer of the sample onto the assay region, for example by providing one or more actuators which, after the micro sampler and/or lancet and/or transfer element has received the sample, press it onto and/or introduce it into the vicinity of the at least one assay region so that the sample is transferred onto the at least one assay region. Various embodiments will be described in detail below.

In particular, the analysis magazine can be designed such that it provides a plurality of analysis aids, for example a plurality of analysis aids of the same type, in each of the possible orientations, for example in each orientation a same number of analysis aids. As indicated above, the analysis cartridges are preferably designed such that different partial cartridges can interact with the same interface of the analysis system in their respective application orientations, so that different interfaces do not have to be reserved in the analysis system for different partial cartridges. The interface may for example comprise: mechanical interfaces, for example, for cyclically moving the individual chambers of each partial magazine and/or for mechanically coupling to an analysis magazine and/or an analysis aid, for example for the purpose of carrying out a sample extraction movement; and/or a measurement interface, for example an optical and/or electrical measurement interface. The analysis system, in particular the interface, can have at least one measuring system, which can be designed to interact with an assay element for detecting at least one analyte. The analysis cartridge can then be configured such that the test element interacts with the same measuring system after the orientation change, without the measuring system having to be substantially adapted to the reoriented cartridge. For example, a certain application position and/or application plane of the analysis system can be provided, wherein the measuring system can interact with the analysis aids (e.g. assay elements and/or assay areas) of the chambers of the partial cartridge which is located exactly in this application position. Thus, for example, the same detector can be used for all test elements and/or test fields of all chambers of all partial cartridges.

The measuring system can be adapted to the design of the analysis cartridge and/or the test element. If these test elements are optical test elements, i.e. test elements which, in cooperation with at least one analyte, change at least one optically detectable property, they can be optical measuring systems. A measuring system of this type may, for example, comprise at least one optical detector, by means of which optical properties can be detected. Additional elements may also be included, such as one or more illumination devices and/or one or more optical systems. Alternatively or additionally, other types of detection may be used, such as electrochemical detection. For this purpose, for example, corresponding electrical and/or electronic measuring devices can be provided, for example, for carrying out an amperometric measurement at the test element.

For example, the measuring system can be designed to interact in at least one application position with at least one assay element located in the at least one application position and/or with a corresponding chamber in the application position. The application position in which the measurement is carried out can be completely or partially identical to the application position in which the sample extraction movement can be carried out. In principle, however, other embodiments are also possible, for example sample removal movements and measurements in different application positions.

In the described embodiment according to the invention, the measuring system can be designed in particular for carrying out measurements with the aid of the same measuring system, even after the orientation transformation has been carried out. In this way, the installation space of the analysis system can be saved and the analysis system can be significantly simplified. In order to make this possible, the analysis magazine can be designed, for example, such that even after the orientation change, the different orientations (for example, analysis aids in different aid planes) are again stored essentially identically relative to one another, so that, for example, one chamber and/or one analysis aid is again arranged in at least one application position.

As already described above, the analysis cartridge preferably has a plurality of properties with respect to its size, in particular with respect to its packing density. In principle, the dimensions mentioned above or smaller, which are directly or indirectly dependent on the filling density, can also be achieved without the above-described design of the analysis cartridge as an inverted cartridge with at least two possible orientations. Accordingly, in a second, parallel aspect of the invention, analysis cartridges are generally proposed which can be designed in particular, but not necessarily, according to one or more of the above-described embodiments. However, other embodiments are also possible, in particular those in which the analysis cartridge is not designed as a flip cartridge or a cartridge with two possible orientations. As is also shown in the dependent claims, the additional features of the preferred embodiments of the first aspect described above can also be implemented in the second aspect of the invention, in particular independently of the first aspect.

The analytical storage cartridge according to the second aspect of the invention has at least two chambers in which the analytical aids can be accommodated. An analysis aid is housed in at least one of the chambers. The analysis aids each comprise at least one test element with at least one test chemical for detecting at least one analyte in a liquid sample, in particular a body fluid.

In conventional analytical cartridges and test elements, in particular for the detection of glucose, test chemicals are often used which are sensitive with respect to the humidity of the air and which, when exposed to air for a long time, can deteriorate their function or even lose their function completely. Accordingly, for example, conventional test strips must be stored in a container in a manner that is sealed with respect to air humidity. The container is typically partially filled with a desiccant (i.e., a material that absorbs moisture, such as activated carbon). Now, if such analytical cartridges and/or analytical aids (e.g. single-use aids (disposables)) are developed in an integrated system, i.e. in which the test elements are packaged individually or in groups, the packaging must also be designed to be moisture-resistant. However, the requirement for tightness against moisture severely limits the choice of potential materials, in particular for the housing. This is particularly relevant in that there are often additional requirements that must be met simultaneously. In most cases, therefore, it is necessary to be able to sterilize the materials used, in particular by means of irradiation with ions. Alternatively or additionally, it is generally not permissible to use the materials used with exhaust gases (ausgasen), in particular after or during the radiation loading by the sterilization process. Again alternatively or additionally, the material used must be suitable for the chosen manufacturing process, for example for an injection molding method and/or another molding process. Again alternatively or additionally, preferably, the material used should be bio-compatible (biokmPatibel) and/or should be bondable and/or protectable. Other requirements may also exist. In particular, the requirement for tightness against moisture is a practically difficult requirement to meet, since most plastics are open to moisture diffusion (particularly at very low wall thicknesses, for example wall thicknesses of less than 1 mm).

Therefore, according to the invention, in a second aspect of the invention (as in a third aspect of the invention which is also described further below), it is proposed that the assay chemical is designed such that it is at least largely stable with respect to environmental influences, in particular with respect to moisture. The assay chemical may be stored, in particular, as a dry chemical (Trockenchemie)In particular on the assay strip. In the context of the present invention, an assay chemical that is substantially stable with respect to environmental influences is understood to be an assay chemical that is stable with respect to air humidity and advantageously also with respect to sterilization methods, in particular sterilization methods using ionizing radiation. Here, what is termed stable is the activity, for example the enzymatic activity of the assay chemical of the analytical aid, when stored at 32 ℃ at a relative air humidity of 85% under normal pressure for a period of three weeksThe reduction is less than 50%, preferably less than 30%, and particularly preferably less than 20%. In principle, the activity can be determined by any method known from the prior art, since, within the scope of the definition given, the ratio of the reduction in activity measured by the method alone to the activity measured by the method before storage or directly after the production of the analytical aids is important. In this case, the activity can be directed in particular to the enzymatic activity of dry chemicals, in particular in assay strips. For example, methods are known which extract enzymes from chemical substances or test strips for measuring the enzyme activity and subsequently determine the activity, for example by means of uv absorption. In this connection, reference may be made, for example, to the writing by h.u. bergmeyer: methods for the analysis of enzymes, chemical publishers, second edition, 1970, page 417 (Methoden der enzymatischen analysis, Verlag Chemie, 2. Aufiage 1970, S.417) or those written by reference to Banauch et al: glucose dehydrogenases (A glucose dehydrogenases for the determination of glucose concentrations in body fluids, Z.Klin. chem. Klin. biochem.1975 Mar; 13 (3): 101-7) are used for determining the glucose content in body fluids. For example, an assay strip with an assay chemical may be manufactured for use in an assay, the enzymatic activity of the enzyme of the assay chemical measured using a common method, followed by storage as described above, and then the same method repeated for measuring the enzymatic activity. The procedure is usually performed using an assay strip or a typical collection of assay chemicals (Kollektiv). For theAlternatively or additionally, a high stability with respect to environmental influences in the form of atmospheric humidity can preferably also be given with respect to environmental influences in the form of radiation (for example gamma radiation and/or beta radiation and/or radiation of other types of ions) which are typically used for the analysis of auxiliary tools and/or for the sterilization of analytical cartridges.

An example of this type of assay chemistry that is stable with respect to environmental influences can be found in document WO2007/012494 a1 already cited above. The assay chemicals shown in this document may also be applied within the scope of the invention, either alone or in combination with one or more of the other assay chemicals. Alternatively or additionally, the assay chemistry may also be designed as disclosed later in the family of applicants from the present patent application (Hause)As described in european patent application document No. EP 08003054.7 or in the subsequently published international patent application document No. PCT/EP 2009/001206.

Thus, the assay chemistry may for example comprise an enzyme and a stable coenzyme (Coenzym), which are stored together. Surprisingly, it was found that long-term stabilities of weeks or months are also possible at high relative humidity or even in the liquid Phase (Phase) and at elevated temperatures with the aid of stable coenzymes. This finding was unexpected because it is known that enzymes have improved short-term stability of several hours in the presence of (in gegenerarto) native (nativ) coenzymes, but have less durability over longer periods of time (Haltbarkeit). Unlike the knowledge with respect to the prior art, it was surprising that the enzyme had a significantly higher long-term stability in the presence of the stabilized coenzyme than in the presence of the natural coenzyme, in particular because the stabilized coenzyme had a lower binding constant to the enzyme (bindungstante) than the natural coenzyme.

The enzymes stabilized by the process according to the invention may in particular be dependent onEnzymes of coenzymes. Suitable enzymes are, for example, dehydrogenases, selected from glucose dehydrogenases (e.c.1.1.1.47), lactate dehydrogenases (e.c.1.1.1.27, 1.1.1.28), malate dehydrogenases (e.c.1.1.1.37), glycerol dehydrogenases (e.c.1.1.1.6), alcohol dehydrogenases (e.c.1.1.1.1), alpha-hydroxybutyrate (alpha-hydroxybutyrate) dehydrogenases, sorbitol dehydrogenases or amino acid dehydrogenases (e.g. L-amino acid dehydrogenases (e.c. 1.4.1.5)). Other suitable enzymes are oxidases (e.g. glucose oxidase (e.c.1.1.3.4) or cholesterol oxidase (e.c.1.1.3.6)) or transaminases (e.g. aspartate or alanine transaminase), 5' nucleotidases or sarcosine kinases. Preferably, the enzyme is glucose dehydrogenase.

The use of variant glucose dehydrogenases has proven to be particularly preferred. The term "variant" as used in the context of the present document relates to genetically altered variants of the native enzyme which, with the same number of amino acids, have an altered amino acid sequence relative to the wild-type (Wildtyp) enzyme, i.e.differ from the wild-type enzyme in at least one amino acid. The variation(s) can be introduced in a position-specific (ortsspezifsch) or non-position-specific manner, preferably in a position-specific manner, using recombinant methods known in the specialist field, wherein, corresponding to the respective requirements and conditions, at least one amino acid exchange is brought about within the amino acid sequence of the native enzyme. It is particularly preferred that the variant has an increased thermal or hydrolytic stability relative to the wild-type enzyme.

The variant glucose dehydrogenase may comprise an amino acid(s) that is (are) altered relative to a corresponding wild-type glucose dehydrogenase at any position in its amino acid sequence. Preferably, the variant glucose dehydrogenase comprises a variation at least one of positions 96, 170 and 252 of the amino acid sequence of the wild-type glucose dehydrogenase, wherein a variation with a variation at positions 96 and 170 or a variation at positions 170 and 252 is particularly preferred. It has proven advantageous if, in addition to this variant, the variant glucose dehydrogenase does not comprise any further variants.

In principle, the variations at positions 96, 170 and 252 can include any amino acid exchange, which leads to stabilization of the wild-type enzyme, for example an increase in thermal or hydrolytic stability. Preferably, the variation at position 96 comprises an amino acid exchange of glutamic acid to glycine, whereas for position 170 an amino acid exchange of glutamic acid to arginine or lysine, in particular an amino acid exchange of glutamic acid to lysine, is preferred. As for the variation at position 252, it preferably includes an amino acid exchange of lysine to leucine.

A variant glucose dehydrogenase can be obtained by variation of a wild-type glucose dehydrogenase from any biological source, wherein, within the scope of the present invention, the term "biological source" encompasses not only prokaryotes (e.g.bacteria) but also eukaryotes (e.g.mammals or other animals). Preferably, the wild-type glucose dehydrogenase is from a bacterium, wherein particularly preferably a glucose dehydrogenase from Bacillus megaterium, Bacillus subtilis or Bacillus thuringiensis, in particular from Bacillus subtilis.

In a particularly preferred embodiment of the invention, the variant glucose dehydrogenase is a glucose dehydrogenase obtained by variation of a wild-type glucose dehydrogenase from Bacillus subtilis, which has the amino acid sequence shown in SEQ ID NO: 1(GlucDH _ E96G _ E170K) or SEQ ID NO: 2(GlucDH _ E170K _ K252L).

Preferably, a stabilized coenzyme is a coenzyme that is chemically altered relative to a native coenzyme, which has a higher stability (e.g., hydrolytic stability) as compared to the native coenzyme. Preferably, the stabilized coenzyme is stable to hydrolysis under assay conditions. A stable coenzyme may have a smaller binding constant for the enzyme compared to a native coenzyme, for example, reduced to 1/2 or less (umden Faktor von 2 der mehr) binding constant.

Preferred examples for stabilized coenzymes are stabilized derivatives of nicotinamide adenine dinucleotide (NAD/NADH) or nicotinamide adenine dinucleotide phosphate (NADP/NADPH), or shortened (verkurzen) NAD derivatives, e.g.without AMP moieties or with non-nucleoside residues (Resten), e.g.hydrophobic residues. In the context of the present invention, preference is likewise given to compounds of the formula (I) as stable coenzymes.

Preferred stable derivatives of NAD/NADH or NADP/NADPH are described in the references mentioned before, to which explicit reference is made here to the disclosure thereof. Particularly preferred stable coenzymes are described in documents WO2007/012494 or US 11/460,366, the disclosures of which are expressly incorporated herein by reference. Particularly preferably, the stable coenzyme is selected from compounds with the general formula (II):

wherein the content of the first and second substances,

a ═ adenine or the like,

t is independently O, S,

u is OH, SH, BH independently₃ ^-，BCNH₂ ^-，

V ═ OH or a phosphate group (phosphatgreppe), or two groups forming cyclic phosphate groups, each independently;

W＝COOR，CON(R)₂，COR，CSN(R)₂wherein R is each independently H or C₁-C₂-Alkyl，

X¹，X²Independently of each other O, CH₂，CHCH₃，C(CH₃)₂，NH，NCH₃，

Y＝NH，S，O，CH₂，

Z is a linear or cyclic organic residue,

with the accompanying instructions: z and pyridine residues are not bound by a glycosidic compound (glycocidischeVerbindung) or a salt thereof or an optionally reduced form thereof.

In the compounds of formula (II), preferably Z is a linear residue with 4 to 6C atoms, preferably 4C atoms, wherein it is possible to replace 1 or 2C atoms by one or more heteroatoms (Heteroatom) selected from O, S and N, if appropriate, or Z is a cyclic group comprising 5 or 6C atoms (cyclo-che Gruppe) which may comprise heteroatoms selected from O, S and N and which may comprise one or more substituents (substient), if appropriate, and the residue CR⁴ ₂Wherein, CR⁴ ₂To a cyclic group and X²Wherein R is⁴H, F, Cl, CH₃。

Particularly preferably, Z is a saturated or unsaturated carbocyclic or heterocyclic pentacyclic ring, especially a compound of the general formula (III),

wherein, in R^5′And R^5″There may be a single bond or a double bond therebetween, wherein,

R⁴h, F, Cl, CH₃，

R⁵＝CR⁴ ₂，

Wherein R is^5′＝O，S，NH，NC₁-C₂-Alkyl，CR⁴ ₂，CHOH，CHOCH₃And an

R^5″＝CR⁴ ₂，CHOH，CHOCH₃When in R^5′And R^5″When a single bond is present between them,

and

wherein R is^5′＝R^5″＝CR⁴When in R^5′And R^5″When a double bond is present between, and R⁶，R^6′Independent CH or CCH₃。

In a preferred embodiment, the compounds according to the invention comprise adenine or an adenine analogue (analga) (e.g. C)₈-and N₆-alternative adenine, Deaza-modifications (such as 7-Deaza) or aza-modifications (azavariate) (such as 8-aza) or combinations (such as 7-Deaza or 8-aza) or carbocyclic analogs (such as m-mycin) wherein halogen, C-ring may be utilized in the 7-position₁-C₆-alkynyl (Alkinyl), -Alkenyl (Alkinyl) or-Alkyl (Alkyl) instead of the 7-Deaza variant.

In another preferred embodiment, the compound comprises an adenosine analogue instead of ribose, which comprises for example 2-methoxydeoxyribose, 2' -fluorodeoxyribose, hexitol, altritol or polycyclic analogues, such as bicyclic-, LNA-and tricyclic sugars.

In particular, in the compounds of the formula (II), it is also possible to replace the (bis) Phosphatsauerstoff isotopically, for example by S^-Or BH₃ ^-In place of O^-Or by NH, NCH₃Or CH₂O is substituted and O is substituted by S.

In the compounds according to the invention of formula (II), W is preferably CONH₂Or COCH₃。

In the radical of the formula (III), R⁵Preferably CH₂. Furthermore, it is preferred that from CH₂R is selected from CHOH and NH^5′. In a particularly preferred embodiment, R^5′And R^5″Are respectively CHOH. In a further preferred embodiment, R^5′Is NH and R^5″Is CH₂。

In a most preferred embodiment, the stable coenzyme is carbanad (carbanad).

In particular, preferred assay chemicals are designed such that the enzymes contained therein are long-term stabilized. This means that the enzyme stabilized with the stabilized coenzyme (e.g. as dry substance) is stored for a duration of e.g. at least 2 weeks, preferably at least 4 weeks, and preferably at least 8 weeks therefrom, and wherein the decrease in enzyme activity relative to the initial value of the enzyme activity is preferably less than 50%, particularly preferably less than 30% and most preferably less than 20%.

Furthermore, the assay chemistry can be designed such that the enzyme stabilized with the stabilized coenzyme is stored at elevated temperatures, for example at a temperature of at least 20 ℃, preferably at least 25 ℃ and particularly preferably at 30 ℃. Preferably, the enzymatic activity is reduced by less than 50%, particularly preferably by less than 30% and most preferably by less than 20% relative to its initial value.

By means of the stabilization according to the invention, it is possible to store enzymes stabilized with stabilized coenzymes also without drying agent, as indicated above, for a long time and/or as indicated above, at high temperatures. Furthermore, even if the stabilized enzyme is stored at high relative air humidity, for example at a relative air humidity of at least 50%, the enzyme activity preferably decreases by less than 50%, particularly preferably by less than 30% and most preferably by less than 20% relative to its initial value.

On the one hand, storage of enzymes stabilized with stable coenzymes can be carried out as dry substances and on the other hand in the liquid phase. Preferably, the stabilized enzyme is stored on or in an assay element, which is suitable for determining the analyte. In this case, enzymes stabilized with a stable coenzyme may be a constituent of a preferred assay chemistry, which may also contain further constituents, such as salts, buffers (buffer) and the like, if appropriate. Here, preferably, the assay chemistry is media-free (Mediator).

Enzymes stabilized with stabilized co-enzymes are generally useful for detecting analytes, such as parameters in body fluids (e.g., blood, serum, plasma, or urine) or waste water samples or foods.

Any biological or chemical substance can be identified as an analyte, which can be detected by a redox reaction, for example a substance which is a Substrate for a coenzyme-dependent enzyme (Substrate) or the coenzyme-dependent enzyme itself. Preferred examples for the analyte are glucose, lactate, malate, glycerol, ethanol, cholesterol, triglycerides, ascorbic acid, cysteine, glutathione, peptides, urea, ammoniumsalts, salicylates, pyruvates, 5' -nucleotidase, Creatine Kinase (CK), Lactate Dehydrogenase (LDH), carbon dioxide, and the like. Preferably, the analyte is glucose. Particularly preferably, glucose is detected here by means of glucose dehydrogenase (GlucDH).

In principle, the change in the stable coenzyme by reaction with the analyte can be detected in any manner. In principle, all methods known from the prior art can be used for detecting the enzymatic reaction. Preferably, however, the change in the coenzyme is detected by optical means. For example, optical detection methods include measuring absorption, fluorescence, Circular Dichroism (CD), optical rotatory color emission (ORD), refraction, and the like.

An optical detection method preferably used within the scope of the present document is photometry. In order to measure the change of the coenzyme due to the reaction with the analyte in a photometric manner, at the same time at least one additional presence of a medium is required which increases the reactivity of the reduced coenzyme and makes it possible to transfer electrons (Elektron) onto a suitable optical indicator or optical indicator system.

Furthermore, suitable agents for the purposes of the present invention may be nitrosoanilines (e.g., [ (4-nitrosophenyl) imino ] dimethanol-hydrochloride), quinones (e.g., phenanthrenequinones (phenanthrolinchinones), benzo [ h ] quinolinequinone), diaziridines (e.g., 1- (3-carboxypropoxy) -5-ethyldiazanthrene-trifluoromethanesulfonates) and/or diaphorases (EC 1.6.99.2)). Preferred examples for diazophenanthrene quinones include 1, 10-diazophenanthrene-5, 6 quinone, 1, 7-diazophenanthrene-5, 6 quinone, 4, 7-diazophenanthrene-5, 6 quinone, and the N-alkylated or N, N '-dialkylated salts thereof, wherein in the case of the N-alkylated or N, N' -dialkylated salts, halides, trifluormethane esters or other solubility-enhancing anions are preferred as counterions.

Any substance that can be reduced and undergoes a detectable change in its optical properties (e.g., color, fluorescence, scattering (reflection), Transmission (Transmission), polarization, and/or refractive index) upon reduction can be used as an optical indicator or indicator system. The presence and/or the amount of the analyte in the sample can be determined with the naked eye and/or with the aid of a detection device using a photometric display method which is suitable for the person skilled in the art. Preferably, heteropolyacids and in particular 2.18-phosphomolybdic acid are used as optical indicators, which are reduced to the corresponding heteropolyblue.

Particularly preferably, the change in coenzyme is detected by measuring fluorescence. Fluorescence measurements are highly sensitive and make it possible to detect even small concentrations of analytes in miniaturized systems.

Alternatively, the change in the coenzyme can also be detected electrochemically using a suitable assay element, for example an electrochemical assay strip. The precondition for this is again the use of a suitable mediator which can be converted from the reduced coenzyme into the reduced form by electron transfer. The determination of the analyte is carried out by measuring the current required by the medium for the reoxidation reduction, which current is related to the analyte concentration in the sample. Examples of media that can be used for electrochemical measurements include, in particular, the media mentioned above that are used for photometric measurements.

For the detection of analytes, liquid assays can be used, in which the reagents are present, for example, in the form of solutions or suspensions in aqueous or non-aqueous liquids or as powders or lyophilized products (Lyophilisat). However, dry assays may also be used, wherein the reagents are applied to a carrier, assay strip. The carrier may for example comprise an assay strip comprising an absorbent and/or swellable (quellbar) material which is wetted by the sample liquid to be examined.

A particularly preferred assay format involves the use of an enzyme (glucose dehydrogenase with a stabilized NAD-derivative) for the detection of glucose, wherein a reduced coenzyme derivative NADH is formed. The detection of NADH is carried out by optical methods, for example by photometric or fluorometric (fluorometric) determination after UV excitation. A particularly preferred assay system is described in document US 2005/0214891, to which reference is explicitly made.

The assay chemical may especially comprise an enzyme stabilized with a stabilized co-enzyme, wherein the activity of the enzyme has a decrease of less than 50%, especially preferably less than 30% and most preferably less than 20% from its initial value when the stabilized enzyme is stored preferably for at least 2 weeks, especially preferably for at least 4 weeks and most preferably for at least 8 weeks, preferably at a temperature of preferably at least 20 ℃, especially preferably at least 25 ℃ and most preferably at least 30 ℃, if possible at high air humidity and without dry reagents.

Alternatively or additionally, other types of stable assay chemicals may also be used, such as the assay chemicals described in document WO2007/012494 a 1. In principle, the assay chemical may be contained in the assay element in any way. The assay chemistry or element may be adapted for performing a dry or liquid assay. For example, the assay chemical may be applied for this purpose on a suitable carrier material, for example on a plastic and/or ceramic material and/or a paper material.

In a second aspect of the invention, the assay cartridge has a volume per cm³An analysis aid packing density of more than 5 analysis aids, preferably at least 10/cm³Especially at least 16/cm³Preferably at least 25/cm³And is for example 32.3/cm³. This packing density is also preferred in other aspects of the invention. Furthermore, as in other aspects also, in the second aspect of the invention, the analysis cartridge preferably has one or more of the following characteristics: not more than 10cm³Total volume of (d); an outer radius of no more than 5 cm; an inner radius between 0.5cm and 2 cm; a thickness of no more than 1 cm; the number of 10 to 100 analysis aids; at 3cm³To 30cm³The volume in between.

It is particularly preferred that the outer volume of the analysis cartridge (i.e. the volume without taking into account the optional opening or other optional hole in the analysis cartridge) does not exceed 5cm³Preferably 3cm³And particularly preferably 2cm³. For example, the external volume may be 1.94cm³. It is particularly preferred that the empty volume (Leervolumen) of the analysis cartridge (i.e. the total volume of the wells optionally present in the analysis cartridge) does not exceed 0.8cm³Preferably 0.5cm³And particularly preferably 0.4cm³. For example, the void volume may be 0.39cm³. For example, the opening can be an opening in the interior of a disk-shaped analysis cartridge, into which opening, for example, the drive element can engage. The inner space (e.g. chamber) in the interior of the housing should not be comprised in this empty volume. In the context of the present invention, a clear volume is generally understood to mean the outer volume minus the empty volume. In the case of a disk-shaped magazine, a volume is thus obtained which is essentially determined from the diameter and height of the disk, and in the case of a ring-disk-shaped magazine a net volume is obtained which is determined by subtracting the volume of the central recess from the net volume of the corresponding disk. It is accordingly preferred that the clear volume of the magazine, i.e. the external volume minus the empty volume, is not more than 5cm³Particularly preferably 3cm³And especially not more than 2cm³. For example, the net volume may be 1.55cm³。

In the context of the present invention, the packing density is generally understood to mean the number of analytical aids per net volume of the analysis cartridge. However, as explained above, each analysis aid may comprise a plurality of partial aids which can interact with one another, for example as assay sections in each case. Preferably, each analysis aid comprises as part of the aid an assay element with at least one assay chemical. In addition, each analytical aid then comprises at least one lancet as a further partial aid for the generation of a sample of the body fluid sample, which is then applied to the associated test element. If a plurality of analytical aids are included in an analytical aid, but for calculating the packing density, they are commonThe analytical part aid still serves as an analytical aid, for example, a common analytical aid calculated from the test element and the associated lancet. For example, exactly one analytical aid with at least one test element and optionally at least one lancet can be accommodated in each case in one chamber. However, as explained above, other designs are also possible.

Thus, the analysis cartridge can be designed, for example, as a circular disk with an outer diameter of less than 100mm (for example 50mm) and an inner diameter of the recess of a circular disk of less than 50mm (for example 22.5 mm). The analysis cartridge may, for example, have a thickness of less than 5.0mm, for example a thickness of 3.1 mm. Preferably, the analysis magazine may comprise more than 20 analysis aids, for example at least 50 analysis aids or even 100 or more analysis aids. For example, 50 analytical aids each having a test element and optionally additionally each having a lancet can be provided, wherein the test element and the associated lancet each count as an analytical aid, also referred to as a "test portion". For example, one auxiliary tool of this type can be accommodated in each case in one chamber. Accordingly, the packing density can be, for example, at least 50 analysis aids/5 cm³1 analysis auxiliary tool/0.1 cm³Preferably at least 50 analysis aids/3 cm³1 auxiliary tool/0.06 cm³And particularly preferably at least 50 analysis aids/2 cm³1 auxiliary tool/0.04 cm³. For example, the packing density may be 50 analysis aids/1.55 cm³1 auxiliary tool/0.031 cm³. However, other designs of the analysis cartridge than the one designed as a disk are also possible, for example in one or more of the previously described geometries. For example, a design is also possible as a tape magazine, wherein, for example, one chamber of the tape magazine comprises a good reel with unused analytical aids and the other chamber of the tape magazine comprises a bad reel on which used analytical aids can be accommodated.

If stable assay chemicals are used, the moisture impermeable design of the separation of the individual chambers can in principle also be completely dispensed with. In a third likewise parallel aspect of the invention (which can be implemented in one or more of the described embodiments separately or also in combination with the above-mentioned first aspect and/or the above-mentioned second aspect, however, which can also be implemented independently), an analysis cartridge is therefore proposed again which can be constructed, in particular, but not necessarily, according to one or more of the above-described embodiments. However, other embodiments are also possible, in particular those in which the analysis magazine is not designed as a flip magazine or a magazine with two possible orientations according to the first aspect, and/or those in which there is no dimensioning mentioned in the second aspect. In this case, reference may again be made to the above description of preferred additional features of the first and second aspects for a preferred embodiment of an analysis cartridge according to the third aspect of the invention, as is also particularly exemplified in the dependent claims. These additional features may also be implemented in the scope of the third aspect of the invention independently of the other features of the first and/or second aspect.

In a third aspect of the invention, the analysis magazine again has at least two chambers in which analysis aids can be accommodated. An analysis aid is housed in at least one of the chambers. The analysis aids each comprise at least one test element with at least one test chemical for detecting at least one analyte in a liquid sample, in particular a body fluid. The assay chemical is again designed such that it is at least largely stable with respect to environmental influences, in particular with respect to humidity. In a third aspect of the invention, it is proposed that the chambers are designed to be separated from one another in such a way that moisture exchange is possible between the chambers, for example between adjacent chambers. For example, the chamber can have a chamber wall, wherein a gap or other aperture, preferably with an aperture width of not more than 20 microns, in particular not more than 10 microns, is provided in or beside the chamber wall. On the one hand, the width of the holes makes possible an exchange of air humidity between the chambers, but generally also prevents coarser contaminants or bacteria. Alternatively or additionally, a material can be applied for the chamber and/or the housing which has a permeability for water vapor. In a third aspect of the invention, at least one of the chambers of the analysis magazine, in particular of the analysis magazine, is designed such that the analysis aid or a part of the analysis aid is stored in at least one of the chambers after use. In the context of the concept of restocking and possible designs of the analysis cartridge for the purpose of restocking, reference is made to the above description of the first aspect of the invention. In particular, a retaining element can be provided again for retaining the analysis aid or a part of the aid which should be of equal importance in the context of this aspect (for example a lancet or a microsampler) in the open chamber after restocking, for example in a form-fitting and/or force-fitting manner. An assay chemical which is at least largely stable with respect to environmental influences during restocking is clearly particularly advantageous, since in many cases humidity (for example in the form of a liquid sample) is actively introduced into the chamber during restocking. By using an assay chemical that is stable with respect to environmental influences according to the invention, this problem can be avoided compared to conventional assay chemicals.

The above-described second aspect and/or the above-described third aspect of the invention, as well as the described first aspect of the invention, may also advantageously be designed further in different ways.

As shown above, in particular the analytical aids can each comprise a test element with a test chemical, in particular a test chemical that is stable with respect to environmental influences, and a lancet. These partial aids can be stored jointly in the same chamber, for example in a pair of a lancet and a test element in one chamber, or in a plurality of pairs of this type in a common chamber. By using a test chemical that is stable with respect to environmental influences, in particular air humidity and/or radiation, the primary requirement for separate packaging of the lancet and the test element can be eliminated. Furthermore, the need to water-vapor-tightly package the assay chemicals and/or insert a desiccant into the chamber and/or the analysis cartridge may also be eliminated. In this way, a new solution is possible, in particular for an analysis magazine with a combination of lancets and test elements. It is not necessary to store the lancet and the test element separately from one another. Furthermore, as will be explained in more detail below, other materials for the cartridge parts can be considered, since the requirements for radiation stability and vapor tightness are no longer jointly fulfilled at the same time.

Since obstacles between the analysis aids, in particular between the lancet and the test element, can be eliminated, a comparatively compact arrangement of the lancet element and the test element can be achieved, for example in the same chamber of the analysis magazine. For example, the lancet tip may be located closely beside the assay chemical when stored in the chamber, which is also suitable as a location for transferring the sample onto the assay chemical after the sample has been obtained. In this way, the mechanism for actuating the analytical aids can be designed considerably simpler than in conventional analytical magazines, since, for example, additional movements for the purpose of overcoming a second obstacle (obstacle between lancet and test element) can be dispensed with, and since the lancet does not have to be moved into an additional position (anfahren). Unlike the previous solutions with separate packaging of the lancet and the test chemical, it is likewise not necessary to move the test chemical in order to remove it from its packaging. In this case, it is also usually only necessary to bring the lancet into contact with the respective actuator and to move the lancet.

In particular, a high packing density can be achieved in that the analysis aids are stored very densely without the need for a sealed separation between the analysis aids. In this regard, the use of stable assay chemicals is clearly particularly advantageous. Thus, for example, an analysis cartridge can be used which has a housing with a wall thickness of at most 1.2 mm. The wall thickness is understood here to mean the thickness of the housing between the chamber containing the analytical aid and the surroundings or adjacent chambers, in particular at the thinnest points of the housing. It is particularly preferred that the wall thickness is not more than 1.0mm and especially not more than 0.8 mm. For example, the wall thickness may be chosen between 0.3mm and 0.8 mm.

Again alternatively or additionally, the use of a desiccant, such as activated carbon, may be eliminated in the analysis cartridge. Accordingly, it is particularly preferred to design the analytical magazine free of desiccant. In this way, installation space can likewise be saved. A desiccant is to be understood here in general as a substance which can hold a large amount of water, for example a substance which substantially preferably absorbs water. In conventional analytical cartridges at least one chamber is provided with a desiccant. However, according to the invention, it is possible to provide an analysis cartridge in which, in the unused state, only a closed chamber with analysis aids is present, but no open chamber with desiccant is present.

Furthermore, better and more precise connection techniques for producing the housing can also be used, in particular when using assay chemicals which are at least largely stable with respect to environmental influences. As will also be explained in detail, it is therefore particularly preferred if the analysis cartridge has a housing with at least two parts, in particular at least two cartridge halves. The two components need not be identical here. The housing, in particular the at least two parts, may jointly form at least two chambers. It is particularly preferred that the at least two parts are connected to each other by means of a method which does not use an adhesive. In particular, a method for material-to-material connection without adhesive is provided. The use of at least one laser welding method is particularly preferred due to high precision and low contamination formation. A uniform weld seam with a small width and high accuracy can be achieved with the laser welding solution, wherein the method can be simultaneously well controlled thermally (thermiisch) and localized and can be carried out practically contamination-free.

In particular, provision is made for a first of the at least two components to be designed transparent and for a second of the at least two components to be designed absorbent (absorbed) when using a laser welding method. In this case, the at least two components can preferably have the same basic material, but each have a different absorption for light in the visible and/or infrared and/or ultraviolet spectrum. For example, the at least two components can have different absorbencies in the spectrum between 500 and 1200nm, in particular in the spectrum between 700 and 1100nm or 700 and 1000nm, in which the customary lasers for laser welding (for example semiconductor lasers and/or Nd: YAG lasers) emit radiation (emittieren). In order to achieve different transparency or absorption of the at least two components, the basic material of the components may be differently colored, for example by doping the basic material (e.g. polycarbonate, PC) of one of the components with a dye to reduce the transparency.

If a welding method is used to connect the at least two components, the weld seam can generally have a width of, for example, at most 0.5mm, in particular at most 0.3mm and particularly preferably at most 0.2 mm. This also helps to increase the packing density. In particular, it is here again clearly advantageous that the assay chemistry is at least largely stable against environmental influences, since in this case the moisture transfer from one chamber to the other is largely irrelevant.

In general, a wide variety of materials can be used for the housing, in particular for at least two parts of the housing, for example for two magazine halves. Thermoplastic plastics are particularly suitable. However, a particular advantage of the invention is that, in particular in the case of the use of assay chemicals which are at least largely stable with respect to environmental influences, the plastic does not have to meet particular requirements with regard to impermeability with respect to moisture. Thus, for example, a material having permeability to water vapor may also be used. Accordingly, the selection and shaping of the plastic (Gestalung) can be carried out according to other criteria, for example according to the processability in a particular shaping process (for example injection molding). Cost effective materials may also be used. For example, one or more of the following plastics may be used: PC (polycarbonate), ABS (acrylonitrile-butadiene-styrene), COC (cyclic olefin-copolymer), PMMA (polymethyl methacrylate), PS (polystyrene), PET (polyethylene terephthalate). These materials have advantages in terms of their processability and/or in terms of their cost, but they are not usable in principle very well when the requirements for vapor tightness must also be met.

For example, PC has a high resistance to radiation of ions, and a high transparency to a wide spectrum. It is a cost-effective bulk material (Massenwerkstoff), however it has a relatively high permeability to water vapor. However, since in the context of the present invention, in particular in the case of the use of stable assay chemicals, the permeability is largely irrelevant in principle, and since in practice the processing properties of the material are particularly good, this material is particularly preferred in the context of the present invention.

ABS can be processed very well and can be injection molded particularly well, so that the use of this material is also advantageous. The material also has good transparency over a broad spectrum and low cost.

COC, although having high transparency in a broad spectrum from ultraviolet to infrared light and providing good vapor blocking, is relatively expensive and only to a certain extent stable with respect to the irradiation of ions.

PMMA has only little or no intrinsic fluorescence in the ultraviolet spectrum and has good transparency over a broad spectrum. Within the scope of the invention, particularly in the case of the use of stable assay chemicals, the high vapor permeability of the material can be tolerated and is a cost-effective material. Therefore, the material can also be advantageously applied within the scope of the present invention.

PS can be processed well, in particular by the injection molding process. Which has good transparency for a broad spectrum. Furthermore, it is a cost effective bulk material. Thus, in general, the material can also be used well within the scope of the present invention.

With this expanded material selectivity, which is no longer limited by the requirement for vapor permeability, it is possible in principle to connect at least two parts of the housing of the analysis cartridge by means of laser welding instead of the conventional ultrasonic welding and/or adhesive methods (which remain for opaque materials). Especially when this component absorbs light for the laser wavelength (for example by corresponding dyeing and/or doping), and wherein the other component is designed to be transparent or more transparent, it is possible to weld the same materials, for example PC to PC and/or COC to COC, etc., very simply, for example by means of a laser. Although parts which are not transparent to radiation (durchtrahlen) can in principle also be irradiated in such a way that welding is possible, the weld seam is generally rougher and requires more space. On the contrary, at high transparency and smooth surfaces of the parts to be interconnected, very narrow welds are obtained, for example with the above-mentioned width of 0.3 mm. The very small weld seam allows the analysis cartridge to be designed very small, for example with the preferred packing densities described above. Furthermore, dust formation during laser welding, which is often present in other welding methods, for example in ultrasonic welding, can be avoided. Furthermore, no vibrations occur, which can bring the structure or the components of the analysis cartridge into resonance. Nor is any additional material, such as an adhesive, required, which may contaminate the interior of the chamber and/or the analytical aids, thereby compromising the hydrophilicity of the lancet or microsampler, for example.

In particular, by using laser welding and/or preferably plastic, new methods for closing and/or covering analytical cartridges (for example for covering processed analytical cartridges) are also possible. The thermally bondable substances are used in many cases up to nowThe membrane closes the assay cartridge. However, the thermal adhesive used here may affect the analysis assistance tool. Thus, vapors such as hot adhesive may affect the lancet and/or the microsampler, for example, compromising its hydrophilicity. However, with the proposed invention, it is possible, in particular when using a laser welding method and/or the proposed materials, to alternatively or additionally also use one or more plastic films for covering the analysis cartridge, for example a metal film (for example an aluminum film), which can be used instead of adhesive, for example, by means of laser welding.

In general, newly obtained degrees of freedom are provided in the choice of materials, thereby providing a basis for a significantly more compact system. This is not only relevant in that the analysis cartridge can be designed with a significantly smaller installation space and/or a significantly increased packing density. The analysis cartridge can also be designed in a manner which is significantly simplified and more cost-effective with regard to its manufacture and/or operation.

As shown above, in addition to the analysis cartridge in one or more of the embodiments described above, an analysis system is also proposed for detecting at least one analyte in a body fluid. The analysis system may be, for example, the above-mentioned measuring system or comprise a measuring system of this type. The analysis system is designed to accommodate at least one analysis cartridge in at least two different orientations. The analysis cartridge can be designed in particular according to one or more of the embodiment variants described above.

In this case, however, it is not absolutely necessary in the context of the proposed analysis system that the analysis cartridge is configured to support the analysis aids in the chambers after restocking, but the analysis system can also be realized in such a way that the analysis cartridge does not support the analysis aids in the chambers after restocking. In this case, a support in the chamber after restocking, for example by force fit, in particular by friction fit, can be dispensed with, although this type of support is still preferred. If no support of this type is provided, the analysis aid can be supported in the chamber, for example by a component of the analysis system, for example a wall of a receptacle for an analysis cartridge.

The analysis system can have, for example, a receptacle in which the analysis cartridge can be received in at least two orientations. As indicated above, the analysis system can, for example, provide at least one interface, for example an interface with a mechanical and/or electrical and/or optical function, wherein, for example, the same interface can interact with different partial cartridges in different orientations, for example with partial cartridges in each case, which are located in the application position or in the application orientation in the current orientation of the analysis cartridge and in which an analysis aid can be provided to the analysis system. As indicated above, the mechanical interface can cause, for example, the clocked continuation of the analysis magazine and/or the provision of at least one actuator for coupling to an analysis aid located in the application position and/or the provision of a measuring system for measuring with an assay element of the analysis aid located in the application position or in the application plane. Reference is made to the above description in respect of other possible designs of the analysis system and/or of the analysis cartridge.

Furthermore, the analysis system can be designed to carry out at least one sample extraction movement by means of an analysis aid accommodated in the analysis magazine. The analysis system is also configured to perform a restocking of the analysis assistance tool. For example, the analysis system can be designed to be first coupled to an analysis aid (which may also comprise part of the aid) located in the application position, to carry out a sample extraction movement with the analysis aid, to be subsequently restored and to be subsequently decoupled again from the analysis aid. Other embodiments and alternatives can be found in reference to the above description.

In particular, the analysis system can have at least one application position and/or application plane. An application position or application plane is understood here to be a position or plane in which at least one chamber of the analysis cartridge can be provided, so that the chamber and/or an analysis aid accommodated therein can be used for the detection of an analysis, for example a sample extraction movement and/or a sample analysis. As indicated above, a plurality of application positions, for example in an application plane, can also be provided here. As indicated above, the sample extraction movement and the measurement of the sample may be performed at different locations, for example.

In particular, the analysis system can be set up to access at least one chamber and/or at least one analysis aid in an application position in at least two different orientations of the analysis cartridge and to detect at least one analyte by means of the chamber and/or the analysis aid in the application position. Thus, for example, a coupling for sample removal movement and/or restocking and/or a coupling for measurement purposes, for example by means of electrical and/or optical measurements and/or the like, can be carried out, which can be adapted to the type and operating principle of the assay chemical.

As already indicated above, the analysis cartridge can be designed in particular such that it comprises at least one display element which can provide information about the current orientation to the analysis system. The analysis system may be equipped accordingly for detecting one or more of the following information: analyzing the orientation of the cartridge; the number of analysis aids already used to analyze the magazine in the current orientation; analyzing the number of remaining aids of the magazine in the current orientation; information about the used orientation of the analysis cartridge; information about the orientation of the magazine which is still retained is analyzed. This detection may be performed by means of one or more of the display elements described above, for example. For example, the at least one display element can be designed to be invariable, for example by means of a corresponding rigid element, the display orientation of which is displayed. Alternatively or additionally, however, at least one display element can also be provided, which is designed to be changeable, for example in the form of a changeable mechanism and/or an electronic information carrier. In this way, the display element functioning as an information carrier can be changed, for example before and/or after the use of the chamber and/or the analysis aid, respectively, for example, for updating information of the type described above. Various embodiments are described in detail below. Furthermore, the evaluation system can be designed, in particular, to convey at least one of the mentioned types of information to the user, for example by means of an optical and/or acoustic and/or tactile display.

In particular, the analysis system can be set up such that the user is required to change the orientation of the analysis cartridge. For example, the directional transformation may be performed automatically. However, it is particularly preferred to change the orientation manually. In particular, the analysis system can recognize, for example as a result of at least one of the information described above, that no unused analysis aids are available in the current orientation. Accordingly, the analysis system requires, for example, the user to change the orientation of the analysis cartridge, for example by opening the system housing of the analysis system, removing the analysis cartridge, rotating the analysis cartridge and inserting it into the housing again.

The analysis cartridge and the analysis system according to one or more of the embodiments described above have a series of advantages over known analysis cartridges and known analysis systems. In particular, therefore, an evaluation system can be realized which fully fulfills the described integration concept in which at least two system functions are combined with one another. In particular, the sample extraction and sample analysis system functions can be realized by means of the same analysis cartridge. At the same time, however, the described requirements, in particular the requirements for a microsampler magazine, are met according to the invention in a good manner. Thus, the analyte within the cartridge may be detected qualitatively and/or quantitatively, e.g., optically and/or electrochemically. At the same time, durability of the assay chemical may be ensured due to the possibility of introducing the assay chemical into the interior of the chamber. Since preferably the assay chemicals are arranged in different chambers, respectively, cross-contamination (Querkontination) in a single micro-sampler can be avoided.

At the same time, the analysis cartridge mentioned can be designed in a simple and cost-effective manner. Furthermore, a particularly compact storage form can be ensured, for example by means of a double-housing form. For example, the compact form of storage allows analytical aids, in particular disposables, to be stored one on top of the other. For example, when stored in a disk magazine, the radius of the disk is coordinated with 25 analytical aids. However, due to the double housing form, it is possible to store, for example, 50 disposables when using a correspondingly smaller or constant diameter of the disc. After using 25 disposables, the user may be required to remove and rotate the analysis cartridge accordingly. In this case, the device-side interface can be reserved in a permanent manner, which allows the system to be connected to the analysis magazine for all analysis aids, for example for all 50 analysis aids.

By leaving the optional interface of the analysis system for coupling the analysis cartridge and/or the analysis aids to the analysis system unchanged, a number of advantages result. These advantages are obtained in particular when using the microsamplers mentioned, in which, for example, the assay area can be determined (Vermessung) after being stored in the cartridge housing. Systems of this type generally require precise positioning of, for example, stationary analytical aids (e.g., test elements) accommodated in the magazine housing relative to a measuring system (e.g., a measuring optical unit (Messoptik)). Furthermore, the positioning must always be ensured reproducibly. However, due to the use of an analysis cartridge according to the invention (for example the turning cartridge described above), these interfaces and/or at least one measuring system can be designed to be identical for all orientations and/or to remain unchanged in the analysis system, in particular for all analysis aids. This results in particular advantages for analytical systems based on restocking.

Drawings

Further details and features of the invention emerge from the following description of preferred embodiments, in particular in conjunction with the dependent claims. The individual features can be realized here individually or in a plurality in combination with one another. The present invention is not limited to these examples. These embodiments are schematically shown in the figures. In the individual figures, the same reference numerals denote identical or functionally corresponding elements.

Wherein:

fig. 1 shows a first embodiment of an analysis cartridge according to the invention in the form of a disk cartridge;

fig. 2A to 2D show a second embodiment of a disc cartridge according to the present invention;

FIG. 3 shows an embodiment of a linear assay cartridge; and

fig. 4 shows an embodiment of an analysis system.

Detailed Description

Fig. 1 shows a perspective sectional view of a first exemplary embodiment of an analysis cartridge 110 according to the invention. As explained below, the analysis magazine 110 is here designed as an exemplary inverted magazine according to the first aspect of the invention. Independently of this embodiment, the analysis cartridge 110 according to fig. 1 can also be used in the exemplary embodiments for the second and third aspects of the invention.

Furthermore, a part of the housing 112 of the analysis system 114 is shown in the illustration in fig. 1, with a finger hole116 through which the sample extraction motion can be performed. In the exemplary embodiment shown, analysis cartridge 110 is designed as a flip-over cartridge in the form of a circular disk cartridge and has two auxiliary tool planes 118, 120. In this case, the two auxiliary tool planes 118,120 are each arranged parallel to one another one above the other and extend parallel to the plane of the plate of the analysis magazine 110. The analysis cartridge 110 has a housing 122 with a large circular central aperture 124. In the housing 122, a plurality of chambers 126 are accommodated in each auxiliary tool plane 118, 120. Here, in the embodiment shown, the chambers 126 are arranged radially and equidistantly in the housing 122. In the illustration according to fig. 1, the housing 122 is shown open, so that the chamber 126 of the first auxiliary tool plane 118 is directed upward and open. The chambers 126 of the second auxiliary tool plane 120 are respectively located below the chambers 126 of the first auxiliary tool plane 118 in a half-unit rotation manner. Thus, the analysis magazine 110 can be assembled from two identical half-planes which are fitted opposite each other and are each rotated by half a unit relative to each other (that is to say half an angular spacing of the chambers 126).

In the illustrated embodiment, an analysis aid 128 is housed in the chamber 126. In this case, the individual partial aids 130 are combined to form an analysis aid 128. Here, the first partial auxiliary tool 130 comprises, for each chamber 126, a microsampler 132 stored radially in the chamber 126. Each microsampler 132, in turn, includes a lancet 134 and a capillary element 136 extending radially inward from the lancet 134. At the ends of the microsamplers 132 facing the (zuweisen) central bore 124, the microsamplers 132 each have a coupling element 138, the coupling elements 138 being designed in the form of eyelets in the illustrated embodiment, into which an actuator of the analysis system 114 (not shown in fig. 1) can then engage for carrying out a sample extraction movement.

The chamber 126 is curved in the radial direction. Thus, the microsampler 132 stored in the chamber 126 is bent about an axis perpendicular to its longitudinal extension and parallel to the plane of the analysis cartridge 110. As will also be explained in detail below, the microsampler 132 is preferably made of a metallic material (e.g., a metal plate). Thus, the micro-sampler 132 has some flexibility and is pressed against the chamber walls of the chamber 126 by its restoring force when bent. As a result, a friction fit is created that holds the microsampler 132 in the chamber 126 and must be overcome by the actuators of the analysis system 114 for sample extraction movement as explained further below. After restocking, which is also explained further below, the microsampler 132 is again held in the chamber 126 by a friction fit. As described above, other retention mechanisms may alternatively or additionally be applied. The holding provided in the context of the analysis cartridge 10 according to the invention (optionally, however, also in the context of the analysis system 114) offers the advantage in particular that the analysis aid 128 and/or parts of the aid (for example the microsampler 132) cannot be removed from the chamber 126 after restocking, which can lead to infection risks, hygiene problems or safety problems, for example.

Furthermore, in the exemplary embodiment shown, the analytical aids 128 each have an assay element 140. The test element 140 includes a test chemical 142 in the form of a test zone 144, which in the illustrated embodiment is integrated into the housing 122. Each test field 144 faces the interior of the associated chamber 126 (zuweisen). As explained in detail below, the assay region 144 can be manufactured, for example, by inserting the assay region 144 over an aperture in the housing 122 of the analysis cartridge 110 such that a surface of the assay region 144 faces the interior of the chamber 126. Here, a common assay region may also be used for a plurality or all of the chambers 126, the limits of the assay regions being defined by apertures in the chambers 126, respectively. The test element 140 forms the other part of the analysis aid 130 of the analysis aid 128.

The analysis system 144 is designed to detect at least one analyte in a body fluid by means of the analysis cartridge 110 or the analysis aid 128 accommodated therein. An integrated detection is realized here by means of the microsampler 132, which detection shall be described as an example below. Fig. 4 therefore shows an analysis system 114 in a very schematic embodiment, in which analysis system 114 an analysis cartridge 10 (for example, according to the type shown in fig. 1) is accommodated. For this purpose, the analysis system 114 can have, for example, one or more receptacles in which the analysis cartridges 110 can be accommodated in different orientations and preferably only in these orientations. For example, the receptacle can have at least one receiving well (aufnahmeschach) and/or at least one recess, and can preferably be opened by the user from the outside for inserting the analysis cartridge 110 and/or for changing the orientation of the analysis cartridge 110, for example for rotating the analysis cartridge 110. In the case shown in fig. 4, the analysis system 114 is configured to use the analysis aid 128 of the first aid plane 118. The analysis system 114 may have a plurality of interfaces for using the analysis cartridge 110 or the analysis aids 128 located therein.

Thus, for example, a positioning device 146 can be provided, which is configured to position the analysis cartridge 110 accordingly. The positioning device 146 may comprise, for example, one or more motors or the like, which can act on corresponding transmission elements of the analysis cartridge 110. Furthermore, the analysis system 114 may include one or more actuators 148, 150, which may be disposed, for example, fully or partially, in the central bore 124. Alternatively or additionally, other system components of the analysis system 114 can also be arranged completely or partially in this central bore 124, so that the overall size of the analysis system 114 can be reduced.

Actuators 148, 150 may include, for example, one or more actuator rods 152 and/or tappets and/or pins configured to couple via coupling elements 138 to analysis aid 128 and/or a portion of aid 130 (e.g., microsampler 132) located in application position 154.

The analysis cycle may include, for example, the following steps. First, a new, as yet unused chamber 126 can be positioned in the application position 154 by means of the positioning device 146. The actuator 148 or the actuator rod 152 is then coupled to the analytical aid 128 in this chamber 126, for example, by hooking a hook of the actuator rod 152 into an eye of the coupling element 138. For this purpose, for example, the actuator rod 152 can pass through a screen (Versiegelung) at the side of the chamber 126 facing the central bore 124 in the application position 154. A sample extraction movement ensues, in which the force of the actuator 148 overcomes the friction fit of the microsampler 132 in the chamber 126, by means of which the microsampler 132 is supported. Here, the microsampler 132 is moved toward the finger hole 116 and through the finger hole 116, toward the skin surface of the test subject. This part of the sample extraction motion may also be referred to as a pricking motion. Thereby, the lancet 134 of the analytical aid 128 penetrates the skin of the test subject and produces a sample of blood and/or interstitial fluid. Already in the case of an intrusion and/or in the case of a subsequent return movement of the lancet 134 (again driving the lancet 134 by the actuator 148 or the actuator rod 152), the capillary element 136 collects the sample and transports it in the direction of the capillary (for example of the capillary gap of the capillary element 136). A return movement of the micro-sampler 132 is performed, wherein the micro-sampler 132 is again stored in the chamber 126 in the application position 154. Here, the micro-sampler 132 is bent by the bending of the chamber 126 and the micro-sampler 132 is pressed again against the chamber wall of the chamber 26, so that the friction fit described above is reproduced and the micro-sampler 132 is held again in the chamber 126 after restocking. Alternatively, the friction fit can also occur after restocking, wherein the microsampler 132 can be accommodated, for example, loosely in the chamber 126 before the analysis aid 128 is used. In this case, for example, the position of the microsampler 132 after restocking may be different from the position of the microsampler 132 before the sample extraction movement is carried out, so that, for example, the above-described bending and thus the friction fit only occurs after restocking.

The contained sample has been transferred onto assay region 144 in the interior of chamber 126 during and/or immediately following the collection process. For this purpose, in the interior of the chamber 126, the microsampler 132 is additionally pressed onto the assay region 144 by a second actuator 150 and/or an actuator rod 156 comprised in this actuator 150 for improved transfer of the sample onto the assay region 144. Alternatively or additionally, however, this transmission may also be brought about by a simple approach between the microsampler 132 and the assay region 144, for example by a corresponding shaping of the wall of the chamber 126 and/or by a corresponding movement of the actuator rod 152. Other holes may be provided for this purpose. The outside of the chamber 126 may additionally be shielded for additionally protecting the analysis aids 128 in the interior of the chamber 126.

After the sample is transferred onto the assay region 144, the assay chemistry 142, for example, included in the assay region 144, may undergo a color reaction and/or other detectable reaction, which may be detected or evaluated by means of the measurement system 158 of the analysis system 114. In addition, the analysis system 114 may include other components. Thus, for example, a controller 160 may be included that may, for example, manipulate and/or evaluate the described system components. For example, the controller 160 may also enable communication with a user via an interface 162 (e.g., one or more input/output interfaces) so that the user may, for example, obtain information and/or manipulate the analysis system 114 in a transmittable manner. Furthermore, the analysis cartridge 110 may comprise one or more display elements 164, which may be detected, for example, by means of one or more orientation sensors 166 of the analysis system 114. In this way, for example, the angular position of the analysis cartridge 110 and/or the orientation of the analysis cartridge 110 can be detected.

As described above, the analysis magazine 110 is designed such that, in the exemplary embodiment shown, the analysis aids 128 are arranged offset from one another in different aid planes 118, 120. Accordingly, as can be seen in fig. 1, the test element window 168 of one of the two auxiliary tool planes 118,120 is located between the two chambers 126 of the respective other of the auxiliary tool planes 118, 120. In this way, it is ensured that the back side of the test field 144 in the application position 154 can be viewed by means of the measuring system 150 in a manner that is not influenced by the adjacent chambers 126 of the respective other auxiliary tool planes 118, 120. Thus, the staggered arrangement of the chambers 126 allows two-sided access to the individual active (aktiv) assay elements 140 in the application position 154, i.e., for example from one side through the measuring system 158 (e.g., the evaluation optical system) and from the rear side through the actuator rod 156 (e.g., the corresponding pin), which brings the microsampler 132 into contact with the assay chemical 142 after the sample has been introduced into and removed through the microsampler 132. In this case, the other analytical aids 128 in the analytical magazine 110 are preferably not exposed and remain sterile until use via their respective covers.

In the embodiment according to fig. 1, the microsampler 132 is accommodated in a chamber 126, which chamber 126 can be designed, for example, to be open upwards or downwards. This feature can be important in coupling mechanisms that are positioned out of the plane of the magazine. As described above, for the piercing movement, an actuator rod 152 (e.g., an actuator tappet) can be coupled to the microsampler 132 in a radial direction with respect to the magazine disk of the analysis magazine 110 and can push the microsampler 132 forward and backward in the recess for carrying out the sample extraction movement described above. In order to ensure shelf life, the exterior of the magazine 110 can be completely or at least partially covered by a thin covering (for example in the form of a thin sealing film) which can be easily penetrated, for example, by the actuator rod 152 and/or the lancet 134 of the micro sampler 132.

For example, the sealing film may also cover the test element window 168, which functions as a measurement window. To open the test element window 168, an additional pull-up mechanism may be provided that exposes the test element window 168 prior to each measurement process. This type of mechanism is not shown in the figures, however, it may be provided additionally. This mechanism can be activated, for example, when the analysis of the magazine 110 continues in a clocked manner. To this end, for example, a retractable blade can be lowered into a recess in the test element window 168 and push the membrane aside as the magazine rotates. In a further alternative or additionally applicable embodiment variant, a seeking movement (Suchbewegung) of the actuator tappet in the form of the actuator rod 152 for the coupling element 138 in the microsampler 132, for example in the form of a guide bore (pilotoch) and/or an eye, can also be used, for example, to pull the membrane apart over the entire length in order to release the path of action (Aktuationsweg) beforehand. To this end, the actuator rod 152 can be pushed forward through the membrane, for example, up to the microsampler 132, and then pushed backward until the actuator rod 152 is inserted into the guide bore of the coupling element 138.

The analysis cartridge 110 may, for example, be equipped with a moisture-insensitive assay element 140, for example according to the prior art described above. In this case, the test element window 168 (e.g., the measurement window) can be dispensed with having its membrane already during the manufacturing process, and in order to ensure long-term stability, the entire analysis cartridge 119 is introduced into a sealed outer enclosure (e.g., a membrane bag). Thus, the calculation is started by the user pulling the expiration date (Aufbrauchfrist) of the outer package. In order to hold the microsampler 132 and/or other partial auxiliary tools 130 of the analysis auxiliary tool 128 or the analysis auxiliary tool 128 as a whole in the chamber 126, the chamber 126 can then be provided with a cover disk which, although, for example, overlaps the width of the microsampler 132, allows or makes possible the engagement of the actuator rod 152.

Furthermore, an insertion aid (Einleghilfe) can be provided at the analysis magazine 110, which likewise can be combined in whole or in part, for example, with the display element 164. The insertion aid makes it easier for the user to correctly insert an analysis cartridge 110 designed as a flip-over cartridge. For this purpose, for example, solutions known from the prior art can be used, such as positioning holes, positioning recesses, positioning pins and/or combinations of the already mentioned and/or other elements (these elements are not discussed further here).

It should be noted in general that it is also possible to implement an analysis cartridge 110 without a display element 164, or to implement an analysis cartridge 110 with other display elements 164 which are designed to be fixed or variable. Since, for example, a drive motor can be provided in the analysis system 114, which drives the analysis cartridges 110 through in a clocked manner (durchkten), for example, alternatively or additionally to the use of the display element 164, a count of the clock (Taktung) can provide information about the test processes which have already been carried out and/or the tests which remain. For example, it is also conceivable for an already used orientation of the evaluation magazine 110 to be recognized by a device-side sensor (in particular a light barrier or the like).

Again alternatively or additionally, the display element 164 also offers the possibility of reusing the analysis cartridge 110. Thus, for example, the user can also temporarily (zwischenzeitlich) remove the analysis cartridge 110 from the analysis system 114, for example, in order to provide and/or insert a sufficient amount of fresh analysis aids 128 (e.g., test elements 140) for short-term travel. In this case, the evaluation system 114 can provide status information to the evaluation magazine 110 and/or the evaluation system 114 via a variable display element 164 (which in this case can function, for example, as a variable mechanical and/or electronic information carrier). When a previously used analysis cartridge 110 is inserted into analysis system 114 again, this status information can first be read and analysis cartridge 110 can be introduced into the position of the next fresh analysis aid 128 (for example of the next fresh test element 140) by means of display element 164.

In the illustrated embodiment, the analysis cartridge 110 shown in fig. 1 comprises or consists of two substantially identical cartridge halves, which can be introduced into the coupling one after the other by turning the cartridge over together with the analysis system 114. Although the inverted magazine occupies a similar structural volume as a linearly enlarged magazine, the compact geometry allows a smaller and/or more ergonomic (ergonomisch) structural shape of the analysis system 114 (which may be designed, for example, as a measuring device). For example, in this way, a volume of less than 130ml can be achieved. In this case, an analysis magazine 110 can be realized which is loaded with 50 or more analysis aids 128.

The user can insert the analysis cartridge 110 into the analysis system 114 in accordance with, for example, a marking (e.g., a printed marking, in particular an arrow marking). Here, for example, first the first auxiliary tool plane 118 can be arranged in the application plane 170. In this orientation, analytical aids 128 accommodated in the aid plane 118 in the analytical magazine 110 can be supplied successively to the analytical system 114, for example by cyclically advancing the magazine 110 through a chamber 126 by means of the transport mechanism of the analytical system 114. After a predetermined number of measurements (e.g., 25 measurements), for example, by the number of chambers 126 in the first auxiliary tool plane 118 of the analysis cartridge 110, the capacity of the first cartridge half is exhausted. The user may then obtain system information for the flip analysis cartridge 110, for example, via the interface 162. The user then opens the analysis system 114 by, for example, opening a corresponding shutter or other type of aperture at the housing 112. Thereafter, one half of the already used analysis cartridge 110 can be removed and turned over. Another imprint and/or other marking on the back side of the analysis cartridge 110 may be used to aid in orientation upon reinsertion.

The risk of incorrect insertion can be avoided by analyzing the design of the geometry of the magazine 110. In particular, shapes are conceivable here which disrupt the symmetry of the cartridge within the insertion plane. Furthermore, it can be helpful to detect the use state of the analysis cartridge 110, so that the operator can be given corresponding instructions. Thus, for example, the number N of analysis aids 128 that have been used_usedMay be important. Furthermore, alternatively or additionally, the identification of used cartridge halves may be important. For example, for this information, a display element 164 at the analysis cartridge may be used.

For example, the controller 160 may be programmed (programmable technology) for obtaining and/or evaluating this type of information. In general, a mathematical switching variable (Schalter) H can be introduced, for example, by a corresponding electronic and/or procedural conversion (umetzung). From assay part N which has been used_usedAnd the information of the cartridge half used, e.g. the remaining assay part N can be calculated_left. The following calculation example is based on the cartridge capacity of 2 × 25 assay sectors:

N_left＝(25-N_used)+H×25

if the second magazine half (i.e., the second auxiliary tool plane 120) is enabled, the mathematical switching amount H takes the value (anehmen) H to 0. Otherwise, H is 1. For example, the switching value H can be obtained by means of a sensor, for example by means of an orientation sensor 166, which can read, for example, display elements 164 on different sides of the analysis cartridge 110. In this way, it can be recognized, for example, whether the second cartridge half is activated. The orientation sensor 166 may, for example, look for previous usage traces on active and/or inactive cartridge halves. Thus, the orientation sensor 166 can be arranged not only on the underside of the analysis cartridge 110, as indicated in fig. 4. Alternatively or additionally, the orientation sensor 166 can also be arranged on the opposite side, i.e. on the side facing away from the application plane 170, and for example look for previously used traces there. For example, conventional sensors are suitable for use as orientation sensors, such as, in particular, optical sensors (e.g., gratings or similar optical sensors) and/or capacitive and/or inductive sensors. In principle, other types of sensors can also be applied.

The display element 164 may include, for example, a variable display element 164 that may, for example, change during use. For example, a sealing film (Siegelfolie), in particular a metallic sealing film, can be provided, which can be pressed in (eindhucken) by previous use. Then the incident light, such as the light emitted by the orientation sensor 166, may no longer be properly reflected. Similarly, for example, the measured capacitance (capacitance principle) and/or inductance (coil principle) can be varied and/or a simple storage element, preferably a variable storage element, for example a magnetic storage element, can be applied. Mechanical sensors and/or display elements 164 (e.g., microswitches) are also suitable for identification and are basically known to the person skilled in the art.

The variables H, N mentioned above for the different initial cases are shown by way of example in Table 1_usedAnd N_left. Furthermore, a possible user indication is shown, which may be given to the user, for example, via the interface 162, in particular via one or more display screens. In principle, however, other designs are also possible.

Table 1: example of computational logic for determining the status of a cartridge

The analysis magazine 110 in the exemplary embodiment shown in the figures is therefore designed as an inverted magazine and has two partial magazines in the form of magazine halves, which are designated by reference numerals 172 and 174 below. The magazine halves 172,174 are designed substantially symmetrically to one another. For example, in the analysis magazine 110, after a rotation about an axis parallel to the auxiliary tool planes 118,120, the first magazine half 172 transitions into the second magazine half 174, wherein, if possible, a slight rotation about an axis perpendicular to the auxiliary tool planes 118,120 by the offset angle of the two auxiliary tool planes 118,120 (that is to say by half the angle of the equidistant angular distribution of the chambers 126) can also be supplemented.

The analysis magazine 110, which is designed as a flip magazine, is intended to ensure the sterility of each analysis aid 128, in particular of each microsampler 132, until a puncture is made. For this reason, at least the microsampler 132 can be introduced into the chamber 126, which is designed in particular as a separate chamber and is preferably designed as aIs designed as a chamber impermeable to bacteria. This object is achieved by evaluating the cartridge 110, in particular by evaluating the respective connection technology of the individual components of the housing 122 of the cartridge 110. In particular, joining methods such as adhesive bonding and/or welding, in particular ultrasonic welding and/or laser welding, can be used here. Preferably, the gaps remaining there, for example between adjacent chambers 126 and/or in the housing 122, should have a width of not more than 10 μm to prevent the passage of bacteria. Another purpose of analysis cartridge 110, which is designed as a flip-over cartridge, may be to guarantee the useful life of the enabled package. The above gap sizes are generally not suitable for blocking moisture out of the interior of the housing 122. For this reason, it is preferred that moisture-compatible for flip-cartridge applicationsA stable assay chemical 142, however, is available at the same time. For example, the assay chemistry 142 known as the carba NAD prescription (Rezeptur) can be used here for optical assay evaluation, as is known, for example, from document WO2007/012494 a 1. In principle, however, alternatively or additionally, a sealed housing 122 and/or a housing in which the chambers 126 are sealed from one another and from the environment by an additional covering can also be used.

The analysis cartridge 110 and the analysis system 114 are described above with reference to the particular illustration in fig. 1. However, the principle illustrated can be transferred without problems to other types of turning cartridges, such as the analysis cartridges 110 described below in fig. 2A to 3, which differ substantially in their external geometry. In principle, however, technical features may be interchanged and not fixedly connected to a particular magazine form, so that the above can be adapted in a similar manner to the embodiments described below.

Fig. 2A to 2D therefore show a second exemplary embodiment of an analysis cartridge 110 according to the invention in different views. Thus, fig. 2A shows a perspective view of analysis cartridge 110 in a view obliquely from above, fig. 2B shows a top view of analysis cartridge 110, fig. 2C shows a cross-sectional view of analysis cartridge 110, and fig. 2D shows an exploded view of analysis cartridge 110. As can be seen from these figures, in the second exemplary embodiment, the analysis magazine 110 is likewise a circular, inverted magazine, which essentially has the shape of a circular disk.

The analysis cartridge 110 is shown here in a closed illustration and again has a housing 122 with a single chamber 126 (in the illustration covered by the housing 122). Reference is largely made to the description of figure 1 above in respect of the individual structural elements. In the two auxiliary tool planes 118,120, the chambers 126 are again distributed equidistantly in the housing 122 in a radial orientation, wherein an angular offset (Verwinkelversatz) of half the distribution angle is again realized between the two auxiliary tool planes 118, 120. This can be seen in particular in the illustration in fig. 2A.

In contrast to the analysis magazine 110 according to the exemplary embodiment shown in fig. 1, in the exemplary embodiment according to fig. 2A to 2D, the microsampler 132 is not located in the chamber 126 in an extended manner, but is preferably bent out of its plane at one end (heraussbiegen). Preferably, the chambers 126 are each formed by two hard components that cause the bending. Engagement into the microsampler 132 (which makes possible sample extraction movement and restorability, for example, by means of the actuator rod 152) is effected by means of a hook-shaped tappet of the actuator rod 152, which is driven from below, that is to say from the central bore 124 into the chamber 126. The hook-shaped tappet pushes the microsampler 132 radially outward, wherein the microsampler 132 follows the guide contour of the chamber 126 into the (begeben) extended position and therefore the guide bore of the coupling element 138 (not shown in detail in the figures) runs onto the hook-shaped tappet of the actuator rod 152. Upon retraction, i.e. during the return movement and/or restocking of the sample extraction movement, the microsampler 132 is bent out of the plane again and thus releases the hook-shaped plunger of the actuator rod 152. In principle, however, other coupling and/or uncoupling mechanisms for performing sample extraction movements and/or restocking are also possible.

The holes, which are indicated in the figures by reference numeral 176, are preferably closed with sealing films at the outer and inner edges of the annular analysis cartridge 110, which sealing films can be penetrated internally by the actuator rod 152 and externally by the microsampler 132.

In the perspective view obliquely above in fig. 2A, it can be seen well that half a unit is rotated between the magazine halves 172 and 174. The test element window 168, which functions as a measurement window, is shown in an open manner. In particular, this type of open measurement window is advantageous in combination again with assay chemicals 142 that are stable with respect to environmental influences.

In the sectional illustration according to fig. 2C, a double arrangement of the magazine halves 172,174 can be seen. By rotating the two cartridge halves 172,174 by half a unit, the microsampler 132 can be seen at different positions relative to the cartridge axis. This arrangement again allows the chambers 126 to be staggered (versechlen) on both sides of the disk in such a way that, despite the small thickness of the disk, the wall thickness produced between the chambers is sufficiently large functionally or production-technically.

For example, the chamber 126 is shown in the lower portion of fig. 2C in the application position 154 (compare also fig. 4). In this illustration, the microsampler 132 in the chamber 126 in the application position 154 is at least partially pushed out of the chamber 126. The actuator rod 152 of the actuator 148 causing the ejection is not shown in this illustration. A preferred structure of the analysis cartridge 110 can be taken from the exploded view in fig. 2D. It follows from the illustration that the housing 122 essentially comprises three parts, which may be welded to each other, for example, as shown above. Thus, the housing 122 includes: an upper window-type ring (Fensterring)178 disposed in the uppermost component plane; and a lower window ring 189 disposed in the lowermost component plane. In the middle plane, a lancet ring 182 is arranged, in which the chambers 126 for 2 × 25 microsamplers 132 or microslits are arranged. The chambers 126 are respectively disposed on the upper and lower sides of the lancet ring 182 in a staggered manner with respect to each other. The elements 178, 180 and 182 can be designed, for example, as plastic components, for example as injection-molded components, for example made of one or more thermoplastics.

Identical chemical rings 184 are coupled up and down to the lancet ring 182, respectively, in other planes between the lancet ring 182 and the window rings 178, 180, respectively. The chemical ring 184 may have, for example, a carrier film, such as a thin plastic film, which is covered with the assay chemical 142 on the side facing the chamber 126. The chemical ring 184 thus forms a continuous assay region 144 for all chambers 126 of the auxiliary tool planes 118,120, wherein the regions of the assay region 144 facing the chambers 126 each form individual assay regions 144 and thus form part of the auxiliary tools 130 of the analysis auxiliary tool 128.

To transfer the sample from the capillary element 136 (not shown in the figures) of the micro-sampler 132 to the assay chemistry 142 of the assay region 144 in the chamber 126, a pressing mechanism may again be provided similar to that shown in FIG. 4. This pressing can be performed, for example, again through a separate pressing hole. Preferably, however, the pressing is done from the side of the test element window 168 from which the measurement is also taken. The small film thickness of the carrier film of the chemical ring 184 allows the membrane clamped in its assay element window 168 to be pressed with little force onto the micro-sampler 132 located in its chamber 126 in order to establish contact between the collected sample and the assay chemistry 142.

The analysis cartridge 110 is closed off by two, for example, essentially identically designed, window-shaped rings 178 and 180. However, additional sealing elements may also be provided. For example, sealing membranes may be disposed at the outer and inner peripheries, the sealing membranes enclosing the chamber holes 176 (see fig. 2A). The sealing film is not shown in the figures.

The advantage of the arrangement according to fig. 2A to 2D is, in particular, the simple production of the different elements of the housing 122. Both the lancet ring 182 and the window rings 178, 180 can be produced as simple injection-molded parts which can be produced in large numbers and with high stability. The chemical ring 184 may be punched out of a common coated film, for example. All rings can be centered, aligned and fitted, for example, by a central axis.

The individual ring elements of the housing 122 are preferably designed in such a way that they can be connected using common production methods and that the smallest possible play is produced here. In particular, gap widths of not more than 10 μm can be produced again, gaps below the mentioned diameters or widths being distinguished by their bacterial impermeability and thus at least largely excluding cross-contamination between used and unused chambers 126 or microsamplers 132. Typical joining methods such as gluing, ultrasonic welding, laser welding, cold sealing (kaltvestemen) or similar techniques are known in principle from the prior art and can also be used within the scope of the invention. In addition, additional auxiliary structures can also be applied to the magazine part of the housing 122, if they are advantageous for the respective connection method.

Fig. 3 shows a third exemplary embodiment of an analysis cartridge 110, which analysis cartridge 110 can be used, for example, again in an analysis system with a design similar to analysis system 114 shown in fig. 4. The analysis magazine 110, which is shown in perspective illustration here as a linear, inverted magazine.

The embodiments shown above are described substantially with reference to the analysis aid 128 with the optical assay chemistry 142. However, other detection methods can also be applied alternatively or additionally to the optical evaluation. The analysis cartridge 110 shown in fig. 3 is therefore used, for example, for an auxiliary tool 128, which auxiliary tool 128 is evaluated according to an electrochemical measurement method. The optical evaluation and thus the test element window 168 can be eliminated.

The analysis aid 128 again comprises a microsampler 132 with a lancet 134, which faces a chamber aperture 176 pointing forward in fig. 3. The microsampler 132 is arranged, for example, on a strip-shaped carrier. The capillary element 136 of the microsampler 132 can transfer the contained blood onto a test element 140 with test chemical 142 in the form of a test field 144, the test element 140 being able to be arranged via an electrical contact (Kontakte)186 at the end of the analysis aid 128, for example in the form of a strip, opposite the lancet 134.

A coupling mechanism (which is coupled to the coupling element 138 of the analysis aid 128, not shown in detail in fig. 3, for causing the sample removal movement and/or the restocking) can also establish an electrical connection to the analysis aid 128. Alternatively, additional elements can also be provided for establishing the electrical connection. The current flowing at the electrochemical contacts of the test element 140 can be evaluated by the electrical connection. The measuring system 158 in fig. 4 can, for example, be set up for this type of measurement. This type of electrochemical measurement is known from the prior art (e.g. the above mentioned prior art) and is not discussed in depth here. Fig. 3 shows an exemplary analysis aid 128 in the form of an electrochemical microsampler in a vertical orientation in the analysis magazine 10. In principle, however, other arrangements are also possible.

Furthermore, in the embodiment shown in fig. 3, it is not necessary to provide a misalignment between the chambers 126 in the upper and lower magazine halves 172, 174. In this embodiment, the two magazine halves 172,174 are embodied as mirror images of one another. In particular, this has the advantage that the magazine positioning can be carried out, for example, solely by evaluating the housing 122 of the magazine 110, and additional positioning aids can also be dispensed with, for example.

In this case, the inversion (i.e., the change in orientation) of the analysis cartridge 110 for the replacement of the respective used cartridge half 172,174 can be effected in different ways. The arrangement of the analysis aid 128 in the chamber 126 may be matched to this certain type of orientation change or flip. Thus, for example, in the two magazine halves 172,174 or in the two auxiliary tool planes 118,120, the analytical auxiliary tool 128 can be oriented identically, for example, with the lancet 134 pointing toward the front chamber opening 176 in fig. 3. In this case, the tilting takes place about an axis which is oriented parallel to the analytical aid 128 and parallel to the aid plane 118,120, for example, perpendicular to an axis running on the elongate front side in fig. 3. As a result, the analysis cartridge 110 can be tilted over the elongate edge.

Alternatively, the analytical aid 128 can also be arranged in a different manner in the magazine halves 172,174, for example by the lancet 134 being directed backwards in fig. 3 in the second magazine half 174. In this case, for example, during the turning, the analysis magazine 110 is rotated about an axis running perpendicular to the analysis aid 128 and parallel to the aid plane 118,120, for example parallel to the axis running in the longitudinal direction of the linear turning magazine.

In principle, the analysis system 114 interacting with the analysis cartridge 110 according to fig. 3 can be designed similarly to the illustration in fig. 4. In particular, an actuator 148 can be provided again, if appropriate with one or more actuator rods 152 and/or other types of coupling elements, which can be coupled to the analytical aid 128. For example, the application location 154 may be set again, with the coupling being implemented in the application location 154. The sample extraction movement can then be carried out again by means of the actuator 148, including a corresponding restocking. Accordingly, analysis aid 128 may again comprise coupling element 138, for example again a guide bore, an eyelet or the like, to which coupling element 138 actuator 148 and/or actuator rod 152 of actuator 148 may be mechanically coupled. As described above, the mechanical coupling can optionally also be combined with an electrical coupling.

List of reference numerals

110 analysis cartridge

112 casing (System)

114 analysis system

116 finger hole

118 first auxiliary tool plane

120 second auxiliary tool plane

122 casing (storage box)

124 central bore

126 chamber

128 analysis appurtenance

130 part auxiliary tool

132 micro sampler

134 lancet

136 capillary element

138 coupling element

140 assay element

142 assay chemistry

144 assay area

146 positioning device

148 actuator

150 actuator

152 actuator rod

154 application location

156 actuator rod

158 measurement system

160 controller

162 interface

164 display element

166 orientation sensor

168 test element window

170 application plane

172 first cartridge half

174 second cartridge half

176 chamber orifice

178 upper window type ring

180 lower window type ring

182 slight blood pricking needle ring

184 chemical ring

186 electrical contact

Claims (21)

1. An analysis cartridge (110), wherein the analysis cartridge (110) has at least two chambers (126) in which an analysis aid (128) can be accommodated, wherein the analysis aid (128) is accommodated in at least one of the chambers (126), wherein the analysis aid (128) comprises: at least one microsampler (132) for creating at least one hole in the skin of a test subject; and at least one test element (140) having at least one test chemical (142) for detecting at least one analyte in a liquid sample, wherein the test chemical (142) is stable at least with respect to humidity, wherein stable means that the activity of the test chemical (142) of the analysis aid (128) decreases by less than 50% when stored at normal pressure for a period of three weeks at 32 ℃ and 85% relative air humidity, wherein the chambers (126) are designed to be separated from one another in such a way that a humidity exchange between the chambers (126) is possible, wherein the chambers (126) have a chamber wall, wherein gaps or other holes with a hole width of not more than 20 μm are provided in or next to the chamber wall, which on the one hand allow an air humidity exchange between the chambers, while preventing coarser contaminants or bacteria, wherein the analysis cartridge (110) is designed to store the analysis aid (128) again in at least one of the chambers (126) after use.

2. An analysis cartridge (110) according to claim 1, wherein the analysis cartridge (110) is configured to be accommodated in an analysis system (114) in at least two orientations, wherein the analysis cartridge (110) is configured to provide a plurality of analysis aids (128) in each of the orientations to the analysis system (114), wherein at least one sample extraction movement is executable by means of the analysis aids (128), wherein the analysis aids (128) comprise at least one transport element for accommodating a sample of a body fluid and/or for transporting the sample, wherein the analysis cartridge (110) is configured to enable a restocking of the analysis aids (128), wherein the analysis cartridge (110) is configured to support the analysis aids (128) in the chamber (126) after the restocking, wherein the chamber (126) is designed such that the micro-sampler (132) is bent in the chamber (126) and presses the micro-sampler (132) against a chamber wall by a restoring force, wherein the analysis magazine (110) comprises at least two substantially identical partial magazines (172,174), wherein each of the partial magazines comprises a plurality of analysis aids (128) of the same type.

3. The analysis cartridge (110) according to claim 2, wherein the analysis cartridge (110) has symmetry at least in part.

4. The analysis cartridge (110) according to claim 3, wherein the analysis cartridge (110) has symmetry about at least one axis of symmetry.

5. The analysis cartridge (110) according to claim 2, characterized in that the analysis cartridge (110) comprises at least one display element (164), wherein the display element (164) is designed to be detected by the analysis system (114) and to provide at least one piece of information about a current orientation to the analysis system (114).

6. The analysis cartridge (110) according to claim 5, characterized in that the analysis cartridge (110) comprises a number of display elements (164) corresponding to the number of possible orientations.

7. The analysis magazine (110) according to claim 2, characterized in that the analysis magazine (110) has the shape of a circular disk, wherein the analysis aids (128) are oriented in a radial arrangement in the analysis magazine (110), wherein the analysis aids (128) are arranged in different aid planes (118,120) angularly offset from one another.

8. The analysis cartridge (110) according to claim 2, characterized in that the analysis cartridge (110) is set up such that, in all orientations, access is possible from at least two directions to a chamber (126) located in an application position (154) of the analysis system (114) in which an analysis aid can be used by the analysis system and/or to at least one analysis aid (128) accommodated in the chamber (126).

9. The analysis cartridge (110) according to claim 8, characterized in that the analysis cartridge (110) is set up to make it possible to access a chamber (126) located in an application position (154) of the analysis system (114) and/or at least one analysis aid (128) accommodated in the chamber (126) from directions opposite to one another.

10. The analysis cartridge (110) according to claim 2, characterized in that the analysis aid (128) is at least partially designed to receive a sample of a body fluid during the sample extraction movement and to deliver the sample to the test element (140), wherein the delivery of the sample takes place at least partially during the restocking of the analysis aid (128).

11. The analysis cartridge (110) according to any one of claims 2 to 10, wherein the assay chemical (142) is configured to change at least one detectable characteristic in the presence of at least one analyte, wherein the assay chemical (142) is at least partially incorporated in the housing (122) of the analysis cartridge (110).

12. The analysis cartridge (110) of claim 11, wherein the test element (140) carries at least one test area (144).

13. The analysis cartridge (110) of claim 11, wherein the assay chemistry (142) is at least partially incorporated in a wall of the chamber (126).

14. The analysis cartridge (110) of claim 1, wherein the liquid sample is a bodily fluid.

15. The analysis cartridge (110) according to claim 1, wherein the analysis cartridge (110) has a housing (112), wherein the housing (112) has a wall thickness of not more than 1.2 mm.

16. The analysis cartridge (110) according to claim 1, characterized in that the analysis cartridge (110) is designed to be desiccant-free.

17. The analysis cartridge (110) according to claim 1, characterized in that the analysis cartridge (110) has a housing (122) with at least two parts, wherein the at least two parts are connected to each other by a laser welding method, wherein at least one weld is provided with a weld width of at most 0.5 mm.

18. The analysis cartridge (110) of claim 17, wherein the housing carries at least two cartridge halves (172, 174).

19. The analysis cartridge (110) according to claim 1, wherein the analysis cartridge (110) has a housing (122), wherein the housing (122) has a material selected from at least one of the following materials: a polycarbonate; acrylonitrile-butadiene-styrene; a cycloolefin-copolymer; polymethyl methacrylate; polystyrene; polyethylene terephthalate.

20. The analysis cartridge (110) of claim 19, wherein the housing (122) carries at least two components.

21. The analysis cartridge (110) according to claim 1, wherein at least one of the chambers (126) is configured to restock the analysis aid (128) in at least one of the chambers (126) after use.